From access to success in science: An academic-student affairs intervention for undergraduate freshmen biology students

NASA Astrophysics Data System (ADS)

Aldridge, Jacqueline Nouvelle

The first year experience is known to present an array of challenges for traditional college students. In particular, freshmen who major in a STEM discipline have their own unique set of challenges when they transition from high school science and math to college science and math; especially chemistry. As a result, students may encounter negative experiences which lower academic and social confidence. This project was designed as a pilot study intervention for a small group of freshmen biology students who were considered academically at-risk due their math SAT scores. The study occurred during the fall semester involving an enhanced active learning component based on the Peer-led Team Learning (PLTL) general chemistry supplemental pedagogy model, and a biology-focused First Year Experience (FYE). PLTL workshops took place in freshmen residence halls, creating a live-n-learn community environment. Mid-term and final chemistry grades and final math grades were collected to measure academic progress. Self-reporting surveys and journals were used to encourage participants to reconstruct their experiences and perceptions of the study. Descriptive analysis was performed to measure statistical significance between midterm and final grade performance, and a general inductive qualitative method was used to determine academic and social confidence as well as experiences and perceptions of the project. Findings of this project revealed a statistically significant improvement between chemistry midterm and final grades of the sample participants. Although academic confidence did not increase, results reveal that social confidence progressed as the majority of students developed a value for studying in groups.

LONGITUDINAL BIOLOGICAL MONITORING OF ORGANOPHOSPHOROUS PESTICIDE EXPOSURE AMONG CHILDREN LIVING IN AN AGRICULTURAL COMMUNITY. (R825171)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

PORE-SCALE MODELING OF BIOLOGICAL CLOGGING DUE TO AGGREGATE EXPANSION: A MATERIAL MECHANICS APPROACH. (R828772)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

BIOLOGICAL MONITORING SURVEY OF ORGANOPHOSPHORUS PESTICIDE EXPOSURE AMONG PRE-SCHOOL CHILDREN IN THE SEATTLE METROPOLITAN AREA. (R825171)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

SUPERCRITICAL FLUID EXTRACTION AND CLEAN-UP PROCEDURES FOR DETERMINATION OF XENOBIOTICS IN BIOLOGICAL SAMPLES. (R825549C011)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

A BIOLOGICALLY BASED RISK ASSESSMENT FOR VINYL ACETATE-INDUCED CANCER AND NON-CANCER INHALATION TOXICITY. (R828610)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

DESIGN, SYNTHESIS, AND BIOLOGICAL EVALUATION OF MATRIX METALLOPROTEINASE INHIBITORS DERIVED FROM A MODIFIED PROLINE SCAFFOLD. (R826113)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Nitric oxide: cancer target or anticancer agent?

PubMed

Mocellin, Simone

2009-03-01

Despite the improved understanding of nitric oxide (NO) biology and the large amount of preclinical experiments testing its role in cancer development and progression, it is still debated whether NO should be considered a potential anticancer agent or instead a carcinogen. The complexity of NO effects within a cell and the variability of the final biological outcome depending upon NO levels makes it highly challenging to determine the therapeutic value of interfering with the activity of this intriguing gaseous messenger. This uncertainty has so far halted the clinical implementation of NO-based therapeutics in the field of oncology. Accordingly, only an in depth knowledge of the mechanisms leading to experimental tumor regression or progression in response to NO will allow us to exploit this molecule to fight cancer.

Chinese Herbal Medicine Meets Biological Networks of Complex Diseases: A Computational Perspective

PubMed Central

Gu, Shuo

2017-01-01

With the rapid development of cheminformatics, computational biology, and systems biology, great progress has been made recently in the computational research of Chinese herbal medicine with in-depth understanding towards pharmacognosy. This paper summarized these studies in the aspects of computational methods, traditional Chinese medicine (TCM) compound databases, and TCM network pharmacology. Furthermore, we chose arachidonic acid metabolic network as a case study to demonstrate the regulatory function of herbal medicine in the treatment of inflammation at network level. Finally, a computational workflow for the network-based TCM study, derived from our previous successful applications, was proposed. PMID:28690664

Chinese Herbal Medicine Meets Biological Networks of Complex Diseases: A Computational Perspective.

PubMed

Gu, Shuo; Pei, Jianfeng

2017-01-01

With the rapid development of cheminformatics, computational biology, and systems biology, great progress has been made recently in the computational research of Chinese herbal medicine with in-depth understanding towards pharmacognosy. This paper summarized these studies in the aspects of computational methods, traditional Chinese medicine (TCM) compound databases, and TCM network pharmacology. Furthermore, we chose arachidonic acid metabolic network as a case study to demonstrate the regulatory function of herbal medicine in the treatment of inflammation at network level. Finally, a computational workflow for the network-based TCM study, derived from our previous successful applications, was proposed.

PERSISTENCE AND BIOLOGICAL ACTIVITY IN SOIL OF INSECTICIDAL PROTEINS FROM BACILLUS THURINGIENSIS AND OF BACTERIAL DNA BOUND ON CLAYS AND HUMIC ACIDS. (R826107)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Recent Progress on Systems and Synthetic Biology Approaches to Engineer Fungi As Microbial Cell Factories.

PubMed

Amores, Gerardo Ruiz; Guazzaroni, María-Eugenia; Arruda, Letícia Magalhães; Silva-Rocha, Rafael

2016-04-01

Filamentous fungi are remarkable organisms naturally specialized in deconstructing plant biomass and this feature has a tremendous potential for biofuel production from renewable sources. The past decades have been marked by a remarkable progress in the genetic engineering of fungi to generate industry-compatible strains needed for some biotech applications. In this sense, progress in this field has been marked by the utilization of high-throughput techniques to gain deep understanding of the molecular machinery controlling the physiology of these organisms, starting thus the Systems Biology era of fungi. Additionally, genetic engineering has been extensively applied to modify wellcharacterized promoters in order to construct new expression systems with enhanced performance under the conditions of interest. In this review, we discuss some aspects related to significant progress in the understating and engineering of fungi for biotechnological applications, with special focus on the construction of synthetic promoters and circuits in organisms relevant for industry. Different engineering approaches are shown, and their potential and limitations for the construction of complex synthetic circuits in these organisms are examined. Finally, we discuss the impact of engineered promoter architecture in the single-cell behavior of the system, an often-neglected relationship with a tremendous impact in the final performance of the process of interest. We expect to provide here some new directions to drive future research directed to the construction of high-performance, engineered fungal strains working as microbial cell factories.

2012 Gordon Research Conference on Cellular and Molecular Fungal Biology, Final Progress Report

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

Berman, Judith

The Gordon Research Conference on Cellular and Molecular Fungal Biology was held at Holderness School, Holderness New Hampshire, June 17 - 22, 2012. The 2012 Gordon Conference on Cellular and Molecular Fungal Biology (CMFB) will present the latest, cutting-edge research on the exciting and growing field of molecular and cellular aspects of fungal biology. Topics will range from yeast to filamentous fungi, from model systems to economically important organisms, and from saprophytes and commensals to pathogens of plants and animals. The CMFB conference will feature a wide range of topics including systems biology, cell biology and morphogenesis, organismal interactions, genomemore » organisation and regulation, pathogenesis, energy metabolism, biomass production and population genomics. The Conference was well-attended with 136 participants. Gordon Research Conferences does not permit publication of meeting proceedings.« less

Thermotropic Liquid Crystal-Assisted Chemical and Biological Sensors

PubMed Central

Honaker, Lawrence W.; Usol’tseva, Nadezhda; Mann, Elizabeth K.

2017-01-01

In this review article, we analyze recent progress in the application of liquid crystal-assisted advanced functional materials for sensing biological and chemical analytes. Multiple research groups demonstrate substantial interest in liquid crystal (LC) sensing platforms, generating an increasing number of scientific articles. We review trends in implementing LC sensing techniques and identify common problems related to the stability and reliability of the sensing materials as well as to experimental set-ups. Finally, we suggest possible means of bridging scientific findings to viable and attractive LC sensor platforms. PMID:29295530

Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

PubMed

Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

2015-02-01

During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

One hundred questions of importance to the conservation of global biological diversity.

PubMed

Sutherland, W J; Adams, W M; Aronson, R B; Aveling, R; Blackburn, T M; Broad, S; Ceballos, G; Côté, I M; Cowling, R M; Da Fonseca, G A B; Dinerstein, E; Ferraro, P J; Fleishman, E; Gascon, C; Hunter, M; Hutton, J; Kareiva, P; Kuria, A; Macdonald, D W; Mackinnon, K; Madgwick, F J; Mascia, M B; McNeely, J; Milner-Gulland, E J; Moon, S; Morley, C G; Nelson, S; Osborn, D; Pai, M; Parsons, E C M; Peck, L S; Possingham, H; Prior, S V; Pullin, A S; Rands, M R W; Ranganathan, J; Redford, K H; Rodriguez, J P; Seymour, F; Sobel, J; Sodhi, N S; Stott, A; Vance-Borland, K; Watkinson, A R

2009-06-01

We identified 100 scientific questions that, if answered, would have the greatest impact on conservation practice and policy. Representatives from 21 international organizations, regional sections and working groups of the Society for Conservation Biology, and 12 academics, from all continents except Antarctica, compiled 2291 questions of relevance to conservation of biological diversity worldwide. The questions were gathered from 761 individuals through workshops, email requests, and discussions. Voting by email to short-list questions, followed by a 2-day workshop, was used to derive the final list of 100 questions. Most of the final questions were derived through a process of modification and combination as the workshop progressed. The questions are divided into 12 sections: ecosystem functions and services, climate change, technological change, protected areas, ecosystem management and restoration, terrestrial ecosystems, marine ecosystems, freshwater ecosystems, species management, organizational systems and processes, societal context and change, and impacts of conservation interventions. We anticipate that these questions will help identify new directions for researchers and assist funders in directing funds. ©2009 Society for Conservation Biology.

Continuation of Crosscutting Technology Development at Cast

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

Yoon, Roe-Hoan

2012-03-31

This Final Technical Report describes progress made on the sub-projects awarded in the Cooperative Agreement DE-FC26-05NT42457: Continuation of Crosscutting Technology Development at Center for Advanced Separation Technologies (CAST). The final reports for each sub-project are attached in the appendix. Much of the research to be conducted with Cooperative Agreement funds will be longer-term, high-risk, basic research and will be carried out in five broad areas: a) Solid-solid separation b) Solid-liquid separation c) Chemical/Biological Extraction d) Modeling and Control, and e) Environmental Control.

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies

PubMed Central

Kristinsson, Sigurdur Y.

2011-01-01

Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed. PMID:21441462

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies.

PubMed

Korde, Neha; Kristinsson, Sigurdur Y; Landgren, Ola

2011-05-26

Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed.

Sequential chemical-biological processes for the treatment of industrial wastewaters: review of recent progresses and critical assessment.

PubMed

Guieysse, Benoit; Norvill, Zane N

2014-02-28

When direct wastewater biological treatment is unfeasible, a cost- and resource-efficient alternative to direct chemical treatment consists of combining biological treatment with a chemical pre-treatment aiming to convert the hazardous pollutants into more biodegradable compounds. Whereas the principles and advantages of sequential treatment have been demonstrated for a broad range of pollutants and process configurations, recent progresses (2011-present) in the field provide the basis for refining assessment of feasibility, costs, and environmental impacts. This paper thus reviews recent real wastewater demonstrations at pilot and full scale as well as new process configurations. It also discusses new insights on the potential impacts of microbial community dynamics on process feasibility, design and operation. Finally, it sheds light on a critical issue that has not yet been properly addressed in the field: integration requires complex and tailored optimization and, of paramount importance to full-scale application, is sensitive to uncertainty and variability in the inputs used for process design and operation. Future research is therefore critically needed to improve process control and better assess the real potential of sequential chemical-biological processes for industrial wastewater treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

[Progress in the study on diacylgycerol acyltransferase (DGAT)-related genes].

PubMed

Ma, Hai-Ming; Shi, Qi-Shun; Liu, Xiao-Chun

2005-12-01

Diacylgycerol Acyltransferase (DGAT) plays an important role in the formation of lipid in different tissues of biological body. DGAT catalyzes the final step in triacylglycerol (TAG) biosynthesis by converting diacylgycerol (DAG) and fatty acyl-coenzyme A (CoA) into triacylglycerol. This enzyme is coded by both DGAT1 and DGAT2. DGAT1 belongs to the gene family of cholesterol acyltransferase (ACAT). DGAT2 belongs to the gene family of monoacylgycerol acyltransferases (MGAT1). This paper reviewed the structure, location on chromosome and biological effect of DGAT-related genes. The relationship between polymorphism and performance of animal was also discussed.

Live Imaging Followed by Single Cell Tracking to Monitor Cell Biology and the Lineage Progression of Multiple Neural Populations.

PubMed

Gómez-Villafuertes, Rosa; Paniagua-Herranz, Lucía; Gascon, Sergio; de Agustín-Durán, David; Ferreras, María de la O; Gil-Redondo, Juan Carlos; Queipo, María José; Menendez-Mendez, Aida; Pérez-Sen, Ráquel; Delicado, Esmerilda G; Gualix, Javier; Costa, Marcos R; Schroeder, Timm; Miras-Portugal, María Teresa; Ortega, Felipe

2017-12-16

Understanding the mechanisms that control critical biological events of neural cell populations, such as proliferation, differentiation, or cell fate decisions, will be crucial to design therapeutic strategies for many diseases affecting the nervous system. Current methods to track cell populations rely on their final outcomes in still images and they generally fail to provide sufficient temporal resolution to identify behavioral features in single cells. Moreover, variations in cell death, behavioral heterogeneity within a cell population, dilution, spreading, or the low efficiency of the markers used to analyze cells are all important handicaps that will lead to incomplete or incorrect read-outs of the results. Conversely, performing live imaging and single cell tracking under appropriate conditions represents a powerful tool to monitor each of these events. Here, a time-lapse video-microscopy protocol, followed by post-processing, is described to track neural populations with single cell resolution, employing specific software. The methods described enable researchers to address essential questions regarding the cell biology and lineage progression of distinct neural populations.

Fifty Years of Progress, 1937-1987 [Lawrence Berkeley Laboratory (LBL, LBNL)

DOE R&D Accomplishments Database

Budinger, T. F. (ed.)

1987-01-01

This booklet was prepared for the 50th anniversary of medical and biological research at the Donner Laboratory and the Lawrence Berkeley Laboratory of the University of California. The intent is to present historical facts and to highlight important facets of fifty years of accomplishments in medical and biological sciences. A list of selected scientific publications from 1937 to 1960 is included to demonstrate the character and lasting importance of early pioneering work. The organizational concept is to show the research themes starting with the history, then discoveries of medically important radionuclides, then the use of accelerated charged particles in therapy, next human physiology studies then sequentially studies of biology from tissues to macromolecules; and finally studies of the genetic code.

Genome Writing: Current Progress and Related Applications.

PubMed

Wang, Yueqiang; Shen, Yue; Gu, Ying; Zhu, Shida; Yin, Ye

2018-02-01

The ultimate goal of synthetic biology is to build customized cells or organisms to meet specific industrial or medical needs. The most important part of the customized cell is a synthetic genome. Advanced genomic writing technologies are required to build such an artificial genome. Recently, the partially-completed synthetic yeast genome project represents a milestone in this field. In this mini review, we briefly introduce the techniques for de novo genome synthesis and genome editing. Furthermore, we summarize recent research progresses and highlight several applications in the synthetic genome field. Finally, we discuss current challenges and future prospects. Copyright © 2018. Production and hosting by Elsevier B.V.

US Army Institute of Dental Research Annual Progress Report FY80.

DTIC Science & Technology

1980-10-01

indicates that use of the laser technique does result in increased connectiv tissue regeneration and improved resolution of the periodontal defects...connectiv tissue regeneration and improved resolution of the periodontal defects. Final analysis of histologic data on the use of the neodymium laser for in...and 21 Bone Regeneration in Trnumatic Wounds (Pathology) DA OH 6038 Development of Endodontic Procedures for 22 Military Dentistry ( Oral Biology) DA OK

Public-private partnership: a new engine for translational research in neurosciences.

PubMed

Murphy, Declan G M; Goldman, Michel; Loth, Eva; Spooren, Will

2014-11-05

We have made little recent progress developing effective new treatments for neuropsychiatric and neurodevelopmental disorders. Novel molecular mechanisms have been identified, but have not translated into the clinic. We suggest an alternative: combinations of treatments targeting different aspects of final common pathways in biologically defined clinical subgroups. This will require integrated translational neuroscience and international public-private partnerships. Copyright © 2014 Elsevier Inc. All rights reserved.

Pleiotropic biological activities of alternatively spliced TMPRSS2/ERG fusion gene transcripts

PubMed Central

Wang, Jianghua; Cai, Yi; Yu, Wendong; Ren, Chengxi; Spencer, David M.; Ittmann, Michael

2008-01-01

TMPRSS2/ERG gene fusions are found in the majority of prostate cancers; however, there is significant heterogeneity in the 5′ region of the alternatively spliced fusion gene transcripts. We have found that there is also significant heterogeneity within the coding exons as well. There is variable inclusion of a 72-bp exon and other novel alternatively spliced isoforms. To assess the biological significance of these alternatively spliced transcripts, we expressed various transcripts in primary prostatic epithelial cells and in an immortalized prostatic epithelial cell line, PNT1a. The fusion gene transcripts promoted proliferation, invasion and motility with variable activities that depended on the structure of the 5′ region encoding the TMPRSS2/ERG fusion and the presence of the 72-bp exon. Cotransfection of different isoforms further enhanced biological activity, mimicking the situation in vivo, in which multiple isoforms are expressed. Finally, knockdown of the fusion gene in VCaP cells resulted in inhibition of proliferation in vitro and tumor progression in an in vivo orthotopic mice model. Our results indicate that TMPRSS2/ERG fusion isoforms have variable biological activities promoting tumor initiation and progression and are consistent with our previous clinical observations indicating that certain TMPRSS2/ERG fusion isoforms are significantly correlated with more aggressive disease. PMID:18922926

Biomacromolecules as carriers in drug delivery and tissue engineering.

PubMed

Zhang, Yujie; Sun, Tao; Jiang, Chen

2018-01-01

Natural biomacromolecules have attracted increased attention as carriers in biomedicine in recent years because of their inherent biochemical and biophysical properties including renewability, nontoxicity, biocompatibility, biodegradability, long blood circulation time and targeting ability. Recent advances in our understanding of the biological functions of natural-origin biomacromolecules and the progress in the study of biological drug carriers indicate that such carriers may have advantages over synthetic material-based carriers in terms of half-life, stability, safety and ease of manufacture. In this review, we give a brief introduction to the biochemical properties of the widely used biomacromolecule-based carriers such as albumin, lipoproteins and polysaccharides. Then examples from the clinic and in recent laboratory development are summarized. Finally the current challenges and future prospects of present biological carriers are discussed.

Cancer biology and genomics: translating discoveries, transforming pathology.

PubMed

Ladanyi, Marc; Hogendoorn, Pancras C W

2011-01-01

Advances in our understanding of cancer biology and discoveries emerging from cancer genomics are being translated into real clinical benefits for patients with cancer. The 2011 Journal of Pathology Annual Review Issue provides a snapshot of recent rapid progress on multiple fronts in the war on cancer or, more precisely, the wars on cancers. Indeed, perhaps the most notable recent shift is reflected by the sharp increase in understanding the biology of multiple specific cancers and using these new insights to inform rationally targeted therapies, with often striking successes. These recent developments, as reviewed in this issue, show how the long-term investments in basic cancer research are finally beginning to bear fruit. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Marine Polysaccharides in Pharmaceutical Applications: An Overview

PubMed Central

Laurienzo, Paola

2010-01-01

The enormous variety of polysaccharides that can be extracted from marine plants and animal organisms or produced by marine bacteria means that the field of marine polysaccharides is constantly evolving. Recent advances in biological techniques allow high levels of polysaccharides of interest to be produced in vitro. Biotechnology is a powerful tool to obtain polysaccharides from a variety of micro-organisms, by controlling the growth conditions in a bioreactor while tailoring the production of biologically active compounds. Following an overview of the current knowledge on marine polysaccharides, with special attention to potential pharmaceutical applications and to more recent progress on the discovering of new polysaccharides with biological appealing characteristics, this review will focus on possible strategies for chemical or physical modification aimed to tailor the final properties of interest. PMID:20948899

Aquatic Toxic Analysis by Monitoring Fish Behavior Using Computer Vision: A Recent Progress

PubMed Central

Fu, Longwen; Liu, Zuoyi

2018-01-01

Video tracking based biological early warning system achieved a great progress with advanced computer vision and machine learning methods. Ability of video tracking of multiple biological organisms has been largely improved in recent years. Video based behavioral monitoring has become a common tool for acquiring quantified behavioral data for aquatic risk assessment. Investigation of behavioral responses under chemical and environmental stress has been boosted by rapidly developed machine learning and artificial intelligence. In this paper, we introduce the fundamental of video tracking and present the pioneer works in precise tracking of a group of individuals in 2D and 3D space. Technical and practical issues suffered in video tracking are explained. Subsequently, the toxic analysis based on fish behavioral data is summarized. Frequently used computational methods and machine learning are explained with their applications in aquatic toxicity detection and abnormal pattern analysis. Finally, advantages of recent developed deep learning approach in toxic prediction are presented. PMID:29849612

Near-Field Scanning Optical Microscopy of Soft, Biological, or Rough Objects in Aqueous Environment: Challenges and some Remedies to Circumvent

NASA Technical Reports Server (NTRS)

Vikram, C. S.; Witherow, W. K.

1999-01-01

Near-field scanning optical microscopy is an established technique for sub-wavelength spatial resolution in imaging, spectroscopy, material science, surface chemistry, polarimetry, etc. A significant amount of confidence has been established for thin hard specimens in air. However when soft, biological, rough, in aqueous environment object, or a combination is involved, the progress has been slow. The tip-sample mechanical interaction, heat effects to sample, drag effects to the probe, difficulty in controlling tip-sample separation in case of rough objects, light scattering from sample thickness, etc. create problems. Although these problems are not even fully understood, there have been attempts to study them with the aim of performing reliable operations. In this review we describe these attempts. Starting with general problems encountered, various effects like polarization, thermal, and media are covered. The roles of independent tip-sample distance control tools in the relevant situations are then described. Finally progress in fluid cell aspect has been summarized.

[Scientific progress and new biological weapons].

PubMed

Berche, Patrick

2006-02-01

The biological weapons are different from conventional weapons, because living germs hold an extraordinary and predictable potential for multiplication, propagation and genetic variation during their dissemination in a susceptible population. Only natural pathogens (1rst generation weapons) have been used in the past (smallpox virus, plague, anthrax, toxins...). However, new threats are emerging, due to the rapid progress of scientific knowledge and its exponential worldwide diffusion. It is possible to synthesize microorganisms from in silico sequences widely diffused on Internet (poliovirus, influenza...), thus resulting in the accessibility of very dangerous virus confined today in high-security laboratories (virus Ebola...). It is possible also to "improve" pathogens by genetic manipulations, becoming more resistant or virulent (2nd generation weapons). Finally, one can now create de novo new pathogens by molecular breeding (DNA shuffling), potentially highly dangerous for naive populations (3rd generation weapons). Making biological weapons does not require too much technological resources and appears accessible to terrorists, due to low cost and easy use. Although the destructive consequences are difficult to predict, the psychological and social damages should be considerable, because of the highly emotional burden in the population associated to the transgression by man of a taboo of life.

The fractured landscape of RNA-seq alignment: the default in our STARs.

PubMed

Ballouz, Sara; Dobin, Alexander; Gingeras, Thomas R; Gillis, Jesse

2018-06-01

Many tools are available for RNA-seq alignment and expression quantification, with comparative value being hard to establish. Benchmarking assessments often highlight methods' good performance, but are focused on either model data or fail to explain variation in performance. This leaves us to ask, what is the most meaningful way to assess different alignment choices? And importantly, where is there room for progress? In this work, we explore the answers to these two questions by performing an exhaustive assessment of the STAR aligner. We assess STAR's performance across a range of alignment parameters using common metrics, and then on biologically focused tasks. We find technical metrics such as fraction mapping or expression profile correlation to be uninformative, capturing properties unlikely to have any role in biological discovery. Surprisingly, we find that changes in alignment parameters within a wide range have little impact on both technical and biological performance. Yet, when performance finally does break, it happens in difficult regions, such as X-Y paralogs and MHC genes. We believe improved reporting by developers will help establish where results are likely to be robust or fragile, providing a better baseline to establish where methodological progress can still occur.

Genetic Modifiers and Oligogenic Inheritance

PubMed Central

Kousi, Maria; Katsanis, Nicholas

2015-01-01

Despite remarkable progress in the identification of mutations that drive genetic disorders, progress in understanding the effect of genetic background on the penetrance and expressivity of causal alleles has been modest, in part because of the methodological challenges in identifying genetic modifiers. Nonetheless, the progressive discovery of modifier alleles has improved both our interpretative ability and our analytical tools to dissect such phenomena. In this review, we analyze the genetic properties and behaviors of modifiers as derived from studies in patient populations and model organisms and we highlight conceptual and technological tools used to overcome some of the challenges inherent in modifier mapping and cloning. Finally, we discuss how the identification of these modifiers has facilitated the elucidation of biological pathways and holds the potential to improve the clinical predictive value of primary causal mutations and to develop novel drug targets. PMID:26033081

Development of a benthic invertebrate objective for mesotrophic Great Lakes waters

USGS Publications Warehouse

Reynoldson, Trefor B.; Schloesser, Donald W.; Manny, Bruce A.

1989-01-01

A biological indicator of mesotrophic conditions should (1) provide an appropriate and interpretable objective; (2) be achievable if corrective measures are taken (i.e., it should be within the expected environmental range of the system); and (3) allow measurement of progress toward the objective. Historical data from the Great Lakes suggest that population density of the burrowing mayfly, Hexagenia limbata, could provide an appropriate objective, and that the tubificid oligochaete community can be used to evaluate progress toward that objective. Finally, data from other systems show thatHexagenia can return to locations where it was formerly abundant, and therefore is an attainable objective for formerly mesotrophic ecosystems.

Windows on the human body--in vivo high-field magnetic resonance research and applications in medicine and psychology.

PubMed

Moser, Ewald; Meyerspeer, Martin; Fischmeister, Florian Ph S; Grabner, Günther; Bauer, Herbert; Trattnig, Siegfried

2010-01-01

Analogous to the evolution of biological sensor-systems, the progress in "medical sensor-systems", i.e., diagnostic procedures, is paradigmatically described. Outstanding highlights of this progress are magnetic resonance imaging (MRI) and spectroscopy (MRS), which enable non-invasive, in vivo acquisition of morphological, functional, and metabolic information from the human body with unsurpassed quality. Recent achievements in high and ultra-high field MR (at 3 and 7 Tesla) are described, and representative research applications in Medicine and Psychology in Austria are discussed. Finally, an overview of current and prospective research in multi-modal imaging, potential clinical applications, as well as current limitations and challenges is given.

Biologically Enhanced Carbon Sequestration: Research Needs and Opportunities

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

Oldenburg, Curtis; Oldenburg, Curtis M.; Torn, Margaret S.

2008-03-21

Fossil fuel combustion, deforestation, and biomass burning are the dominant contributors to increasing atmospheric carbon dioxide (CO{sub 2}) concentrations and global warming. Many approaches to mitigating CO{sub 2} emissions are being pursued, and among the most promising are terrestrial and geologic carbon sequestration. Recent advances in ecology and microbial biology offer promising new possibilities for enhancing terrestrial and geologic carbon sequestration. A workshop was held October 29, 2007, at Lawrence Berkeley National Laboratory (LBNL) on Biologically Enhanced Carbon Sequestration (BECS). The workshop participants (approximately 30 scientists from California, Illinois, Oregon, Montana, and New Mexico) developed a prioritized list of researchmore » needed to make progress in the development of biological enhancements to improve terrestrial and geologic carbon sequestration. The workshop participants also identified a number of areas of supporting science that are critical to making progress in the fundamental research areas. The purpose of this position paper is to summarize and elaborate upon the findings of the workshop. The paper considers terrestrial and geologic carbon sequestration separately. First, we present a summary in outline form of the research roadmaps for terrestrial and geologic BECS. This outline is elaborated upon in the narrative sections that follow. The narrative sections start with the focused research priorities in each area followed by critical supporting science for biological enhancements as prioritized during the workshop. Finally, Table 1 summarizes the potential significance or 'materiality' of advances in these areas for reducing net greenhouse gas emissions.« less

Yields of biologically significant damage produced in mammalian DNA by irradiation associated with radon decay. Final progress report

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

Ward, J.F.

1994-03-01

The objective of this project was to characterize the difference between damage to DNA caused by alpha particles and by low LET radiation. Estimation of the risk posed by exposure to high LET radiation (such as that from radon) relies at present on epidemiological data, and is therefore largely empirical. This empiricism is evident from the concepts of quality factor or RBE that find use for describing the biological effects of high LET radiation. The author argues that some effort should be made to address the mechanisms of DNA damage by high and low LET forms of radiation, and howmore » these mechanisms might relate to the biological endpoints. This report summarizes the results of the author`s investigations and the current understanding of these mechanisms.« less

Extending the knowledge in histochemistry and cell biology.

PubMed

Heupel, Wolfgang-Moritz; Drenckhahn, Detlev

2010-01-01

Central to modern Histochemistry and Cell Biology stands the need for visualization of cellular and molecular processes. In the past several years, a variety of techniques has been achieved bridging traditional light microscopy, fluorescence microscopy and electron microscopy with powerful software-based post-processing and computer modeling. Researchers now have various tools available to investigate problems of interest from bird's- up to worm's-eye of view, focusing on tissues, cells, proteins or finally single molecules. Applications of new approaches in combination with well-established traditional techniques of mRNA, DNA or protein analysis have led to enlightening and prudent studies which have paved the way toward a better understanding of not only physiological but also pathological processes in the field of cell biology. This review is intended to summarize articles standing for the progress made in "histo-biochemical" techniques and their manifold applications.

[Metabolomics research of medicinal plants].

PubMed

Duan, Li-Xin; Dai, Yun-Tao; Sun, Chao; Chen, Shi-Lin

2016-11-01

Metabolomics is the comprehensively study of chemical processes involving small molecule metabolites. It is an important part of systems biology, and is widely applied in complex traditional Chinese medicine（TCM）system. Metabolites biosynthesized by medicinal plants are the effective basis for TCM. Metabolomics studies of medicinal plants will usher in a new period of vigorous development with the implementation of Herb Genome Program and the development of TCM synthetic biology. This manuscript introduces the recent research progresses of metabolomics technology and the main research contents of metabolomics studies for medicinal plants, including identification and quality evaluation for medicinal plants, cultivars breeding, stress resistance, metabolic pathways, metabolic network, metabolic engineering and synthetic biology researches. The integration of genomics, transcriptomics and metabolomics approaches will finally lay foundation for breeding of medicinal plants, R&D, quality and safety evaluation of innovative drug. Copyright© by the Chinese Pharmaceutical Association.

Use of Mesothelial Cells and Biological Matrices for Tissue Engineering of Simple Epithelium Surrogates.

PubMed

Lachaud, Christian Claude; Rodriguez-Campins, Berta; Hmadcha, Abdelkrim; Soria, Bernat

2015-01-01

Tissue-engineering technologies have progressed rapidly through last decades resulting in the manufacture of quite complex bioartificial tissues with potential use for human organ and tissue regeneration. The manufacture of avascular monolayered tissues such as simple squamous epithelia was initiated a few decades ago and is attracting increasing interest. Their relative morphostructural simplicity makes of their biomimetization a goal, which is currently accessible. The mesothelium is a simple squamous epithelium in nature and is the monolayered tissue lining the walls of large celomic cavities (peritoneal, pericardial, and pleural) and internal organs housed inside. Interestingly, mesothelial cells can be harvested in clinically relevant numbers from several anatomical sources and not less important, they also display high transdifferentiation capacities and are low immunogenic characteristics, which endow these cells with therapeutic interest. Their combination with a suitable scaffold (biocompatible, degradable, and non-immunogenic) may allow the manufacture of tailored serosal membranes biomimetics with potential spanning a wide range of therapeutic applications, principally for the regeneration of simple squamous-like epithelia such as the visceral and parietal mesothelium vascular endothelium and corneal endothelium among others. Herein, we review recent research progresses in mesothelial cells biology and their clinical sources. We make a particular emphasis on reviewing the different types of biological scaffolds suitable for the manufacture of serosal mesothelial membranes biomimetics. Finally, we also review progresses made in mesothelial cells-based therapeutic applications and propose some possible future directions.

Use of Mesothelial Cells and Biological Matrices for Tissue Engineering of Simple Epithelium Surrogates

PubMed Central

Lachaud, Christian Claude; Rodriguez-Campins, Berta; Hmadcha, Abdelkrim; Soria, Bernat

2015-01-01

Tissue-engineering technologies have progressed rapidly through last decades resulting in the manufacture of quite complex bioartificial tissues with potential use for human organ and tissue regeneration. The manufacture of avascular monolayered tissues such as simple squamous epithelia was initiated a few decades ago and is attracting increasing interest. Their relative morphostructural simplicity makes of their biomimetization a goal, which is currently accessible. The mesothelium is a simple squamous epithelium in nature and is the monolayered tissue lining the walls of large celomic cavities (peritoneal, pericardial, and pleural) and internal organs housed inside. Interestingly, mesothelial cells can be harvested in clinically relevant numbers from several anatomical sources and not less important, they also display high transdifferentiation capacities and are low immunogenic characteristics, which endow these cells with therapeutic interest. Their combination with a suitable scaffold (biocompatible, degradable, and non-immunogenic) may allow the manufacture of tailored serosal membranes biomimetics with potential spanning a wide range of therapeutic applications, principally for the regeneration of simple squamous-like epithelia such as the visceral and parietal mesothelium vascular endothelium and corneal endothelium among others. Herein, we review recent research progresses in mesothelial cells biology and their clinical sources. We make a particular emphasis on reviewing the different types of biological scaffolds suitable for the manufacture of serosal mesothelial membranes biomimetics. Finally, we also review progresses made in mesothelial cells-based therapeutic applications and propose some possible future directions. PMID:26347862

Chronic lymphocytic leukemia.

PubMed

Kay, Neil E; Hamblin, Terry J; Jelinek, Diane F; Dewald, Gordon W; Byrd, John C; Farag, Sherif; Lucas, Margaret; Lin, Thomas

2002-01-01

This update of early stage B-cell chronic lymphocytic leukemia (B-CLL) embraces current information on the diagnosis, biology, and intervention required to more fully develop algorithms for management of this disease. Emphasis on early stage is based on the rapid advancement in our understanding of the disease parameters and our increasing ability to predict for a given early stage patient whether there is a need for more aggressive management. In Section I, Dr. Terry Hamblin addresses the nature of the disease, accurate diagnostic procedures, evidence for an early "preclinical" phase, the use of newer prognostic features to distinguish who will be likely to progress or not, and whether it is best to watch or treat early stage disease. In Section II, Dr. Neil Kay and colleagues address the biologic aspects of the disease and how they may relate to disease progression. Review of the newer insights into gene expression, recurring genetic defects, role of cytokines/autocrine pathways, and the interaction of the CLL B cell with the microenvironment are emphasized. The relationship of these events to both trigger disease progression and as opportunities for future therapeutic intervention even in early stage disease is also considered. In Section III, Dr. John Byrd and colleagues review the historical and now current approaches to management of the previously untreated progressive B-CLL patient. They discuss what decision tree could be used in the initial decision to treat a given patient. The use of single agents versus newer combination approaches such as chemoimmunotherapy are discussed here. In addition, the place of marrow transplant and some of the newer antibodies available for treatment of B-CLL are considered. Finally, a challenge to utilize our growing knowledge of the biology of B-CLL in the early stage B-CLL is proffered.

Preclinical Magnetic Resonance Imaging and Systems Biology in Cancer Research

PubMed Central

Albanese, Chris; Rodriguez, Olga C.; VanMeter, John; Fricke, Stanley T.; Rood, Brian R.; Lee, YiChien; Wang, Sean S.; Madhavan, Subha; Gusev, Yuriy; Petricoin, Emanuel F.; Wang, Yue

2014-01-01

Biologically accurate mouse models of human cancer have become important tools for the study of human disease. The anatomical location of various target organs, such as brain, pancreas, and prostate, makes determination of disease status difficult. Imaging modalities, such as magnetic resonance imaging, can greatly enhance diagnosis, and longitudinal imaging of tumor progression is an important source of experimental data. Even in models where the tumors arise in areas that permit visual determination of tumorigenesis, longitudinal anatomical and functional imaging can enhance the scope of studies by facilitating the assessment of biological alterations, (such as changes in angiogenesis, metabolism, cellular invasion) as well as tissue perfusion and diffusion. One of the challenges in preclinical imaging is the development of infrastructural platforms required for integrating in vivo imaging and therapeutic response data with ex vivo pathological and molecular data using a more systems-based multiscale modeling approach. Further challenges exist in integrating these data for computational modeling to better understand the pathobiology of cancer and to better affect its cure. We review the current applications of preclinical imaging and discuss the implications of applying functional imaging to visualize cancer progression and treatment. Finally, we provide new data from an ongoing preclinical drug study demonstrating how multiscale modeling can lead to a more comprehensive understanding of cancer biology and therapy. PMID:23219428

PCSK9: Regulation and Target for Drug Development for Dyslipidemia.

PubMed

Burke, Amy C; Dron, Jacqueline S; Hegele, Robert A; Huff, Murray W

2017-01-06

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted zymogen expressed primarily in the liver. PCSK9 circulates in plasma, binds to cell surface low-density lipoprotein (LDL) receptors, is internalized, and then targets the receptors to lysosomal degradation. Studies of naturally occurring PCSK9 gene variants that caused extreme plasma LDL cholesterol (LDL-C) deviations and altered atherosclerosis risk unleashed a torrent of biological and pharmacological research. Rapid progress in understanding the physiological regulation of PCSK9 was soon translated into commercially available biological inhibitors of PCSK9 that reduced LDL-C levels and likely also cardiovascular outcomes. Here we review the swift evolution of PCSK9 from novel gene to drug target, to animal and human testing, and finally to outcome trials and clinical applications. In addition, we explore how the genetics-guided path to PCSK9 inhibitor development exemplifies a new paradigm in pharmacology. Finally, we consider some potential challenges as PCSK9 inhibition becomes established in the clinic.

Genetic testing for hearing impairment.

PubMed

Topsakal, V; Van Camp, G; Van de Heyning, P

2005-01-01

For some patients, genetic testing can reveal the etiology of their hearing impairment, and can provide evidence for a medical diagnosis. However, a gap between fundamental genetic research on hereditary deafness and clinical otology emerges because of the steadily increasing number of discovered genes for hereditary hearing impairment (HHI) and the comparably low clinical differentiation of the HHIs. In an attempt to keep up with the scientific progress, this article enumerates the indications of genetic testing for HHI from a clinical point of view and describes the most frequently encountered HHIs in Belgium. Domains of recent scientific interest, molecular biological aspects, and some pitfalls with HHIs are highlighted. The overview comprises bilateral congenital hearing loss, late-onset progressive high frequency hearing loss, progressive bilateral cochleo-vestibular deficit, and progressive low frequency hearing loss. Also, several syndromal forms of HHI are summarized, and the availability of genetic tests mentioned. Finally, the requirements for successful linkage analysis, an important genetic research tool for localizing the potential genes of a trait on a chromosome, are briefly described.

[Chemotherapy in epithelial ovarian cancer].

PubMed

Tazi, Y; Pautier, P; Leary, A; Lhomme, C

2013-10-01

Chemotherapy is fundamental in the management of epithelial ovarian carcinomas both for early and advanced stages (rarely surgical treatment alone) and in almost every step of the disease. The reference schema combines carboplatin and paclitaxel intravenously. Intraperitoneal chemotherapy also proved its efficacy after complete surgery for advanced disease and should be reserved to trained teams due to its technical constraints and toxicity issues. Modalities of treatment in relapsed and progressive disease depend mainly on the free interval between this diagnosis and the last dose of platinum. Bevacizumab has proven its effectiveness in prolonging progression-free survival in 1st line setting in association with chemotherapy followed by maintenance and in case of relapse or progression both fore platinum sensitive or resistant disease. Finally, a better understanding of ovarian cancer biology will allow us to consider new molecular-targeted agents guided by the specific characteristics of each patient and each tumor. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Windows on the Human Body – in Vivo High-Field Magnetic Resonance Research and Applications in Medicine and Psychology

PubMed Central

Moser, Ewald; Meyerspeer, Martin; Fischmeister, Florian Ph. S.; Grabner, Günther; Bauer, Herbert; Trattnig, Siegfried

2010-01-01

Analogous to the evolution of biological sensor-systems, the progress in “medical sensor-systems”, i.e., diagnostic procedures, is paradigmatically described. Outstanding highlights of this progress are magnetic resonance imaging (MRI) and spectroscopy (MRS), which enable non-invasive, in vivo acquisition of morphological, functional, and metabolic information from the human body with unsurpassed quality. Recent achievements in high and ultra-high field MR (at 3 and 7 Tesla) are described, and representative research applications in Medicine and Psychology in Austria are discussed. Finally, an overview of current and prospective research in multi-modal imaging, potential clinical applications, as well as current limitations and challenges is given. PMID:22219684

Molecular biology of anal squamous cell carcinoma: implications for future research and clinical intervention.

PubMed

Bernardi, Maria-Pia; Ngan, Samuel Y; Michael, Michael; Lynch, A Craig; Heriot, Alexander G; Ramsay, Robert G; Phillips, Wayne A

2015-12-01

Anal squamous cell carcinoma is a human papillomavirus-related disease, in which no substantial advances in treatment have been made in over 40 years, especially for those patients who develop disease relapse and for whom no surgical options exist. HPV can evade the immune system and its role in disease progression can be exploited in novel immunotherapy platforms. Although several studies have investigated the expression and inactivation (through loss of heterozygosity) of tumour suppressor genes in the pathways to cancer, no clinically valuable biomarkers have emerged. Regulators of apoptosis, including survivin, and agents targeting the PI3K/AKT pathway, offer opportunities for targeted therapy, although robust data are scarce. Additionally, antibody therapy targeting EGFR may prove effective, although its safety profile in combination with standard chemoradiotherapy has proven to be suboptimal. Finally, progress in the treatment of anal cancer has remained stagnant due to a lack of preclinical models, including cell lines and mouse models. In this Review, we discuss the molecular biology of anal squamous cell carcinoma, clinical trials in progress, and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a resource for investigation of new molecular pathways and for testing novel targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

History and conceptual developments in vascular biology and angiogenesis research: a personal view.

PubMed

Bikfalvi, Andreas

2017-11-01

Vascular biology is an important scientific domain that has gradually penetrated many medical and scientific fields. Scientists are most often focused on present problems in their daily scientific work and lack awareness regarding the evolution of their domain throughout history and of how philosophical issues are related to their research field. In this article, I provide a personal view with an attempt to conceptualize vascular development research that articulates lessons taken from history, philosophy, biology and medicine. I discuss selected aspects related to the history and the philosophy of sciences that can be extracted from the study of vascular development and how conceptual progress in this research field has been made. I will analyze paradigm shifts, cross-fertilization of different fields, technological advances and its impact on angiogenesis and discuss issues related to evolutionary biology, proximity of different molecular systems and scientific methodologies. Finally, I discuss briefly my views where the field is heading in the future.

Development and Applications Of Photosensitive Device Systems To Studies Of Biological And Organic Materials

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

Gruner, Sol

2012-01-20

The primary focus of the grant is the development of new x-ray detectors for biological and materials work at synchrotron sources, especially Pixel Array Detectors (PADs), and the training of students via research applications to problems in biophysics and materials science using novel x-ray methods. This Final Progress Report provides a high-level overview of the most important accomplishments. These major areas of accomplishment include: (1) Development and application of x-ray Pixel Array Detectors; (2) Development and application of methods of high pressure x-ray crystallography as applied to proteins; (3) Studies on the synthesis and structure of novel mesophase materials derivedmore » from block co-polymers.« less

Synthetic Biology Expands the Industrial Potential of Yarrowia lipolytica.

PubMed

Markham, Kelly A; Alper, Hal S

2018-06-04

The oleaginous yeast Yarrowia lipolytica is quickly emerging as the most popular non-conventional (i.e., non-model organism) yeast in the bioproduction field. With a high propensity for flux through tricarboxylic acid (TCA) cycle intermediates and biological precursors such as acetyl-CoA and malonyl-CoA, this host is especially well suited to meet our industrial chemical production needs. Recent progress in synthetic biology tool development has greatly enhanced our ability to rewire this organism, with advances in genetic component design, CRISPR technologies, and modular cloning strategies. In this review we investigate recent developments in metabolic engineering and describe how the new tools being developed help to realize the full industrial potential of this host. Finally, we conclude with our vision of the developments that will be necessary to enhance future engineering efforts. Copyright © 2018 Elsevier Ltd. All rights reserved.

Applying ecological and evolutionary theory to cancer: a long and winding road.

PubMed

Thomas, Frédéric; Fisher, Daniel; Fort, Philippe; Marie, Jean-Pierre; Daoust, Simon; Roche, Benjamin; Grunau, Christoph; Cosseau, Céline; Mitta, Guillaume; Baghdiguian, Stephen; Rousset, François; Lassus, Patrice; Assenat, Eric; Grégoire, Damien; Missé, Dorothée; Lorz, Alexander; Billy, Frédérique; Vainchenker, William; Delhommeau, François; Koscielny, Serge; Itzykson, Raphael; Tang, Ruoping; Fava, Fanny; Ballesta, Annabelle; Lepoutre, Thomas; Krasinska, Liliana; Dulic, Vjekoslav; Raynaud, Peggy; Blache, Philippe; Quittau-Prevostel, Corinne; Vignal, Emmanuel; Trauchessec, Hélène; Perthame, Benoit; Clairambault, Jean; Volpert, Vitali; Solary, Eric; Hibner, Urszula; Hochberg, Michael E

2013-01-01

Since the mid 1970s, cancer has been described as a process of Darwinian evolution, with somatic cellular selection and evolution being the fundamental processes leading to malignancy and its many manifestations (neoangiogenesis, evasion of the immune system, metastasis, and resistance to therapies). Historically, little attention has been placed on applications of evolutionary biology to understanding and controlling neoplastic progression and to prevent therapeutic failures. This is now beginning to change, and there is a growing international interest in the interface between cancer and evolutionary biology. The objective of this introduction is first to describe the basic ideas and concepts linking evolutionary biology to cancer. We then present four major fronts where the evolutionary perspective is most developed, namely laboratory and clinical models, mathematical models, databases, and techniques and assays. Finally, we discuss several of the most promising challenges and future prospects in this interdisciplinary research direction in the war against cancer.

Systems healthcare: a holistic paradigm for tomorrow.

PubMed

Fiandaca, Massimo S; Mapstone, Mark; Connors, Elenora; Jacobson, Mireille; Monuki, Edwin S; Malik, Shaista; Macciardi, Fabio; Federoff, Howard J

2017-12-19

Systems healthcare is a holistic approach to health premised on systems biology and medicine. The approach integrates data from molecules, cells, organs, the individual, families, communities, and the natural and man-made environment. Both extrinsic and intrinsic influences constantly challenge the biological networks associated with wellness. Such influences may dysregulate networks and allow pathobiology to evolve, resulting in early clinical presentation that requires astute assessment and timely intervention for successful mitigation. Herein, we describe the components of relevant biological systems and the nature of progression from at-risk to manifest disease. We illustrate the systems approach by examining two relevant clinical examples: Alzheimer's and cardiovascular diseases. The implications of systems healthcare management are examined through the lens of economics, ethics, policy and the law. Finally, we propose the need to develop new educational paradigms to enhance the training of the health professional in an era of systems medicine.

Shadows of complexity: what biological networks reveal about epistasis and pleiotropy

PubMed Central

Tyler, Anna L.; Asselbergs, Folkert W.; Williams, Scott M.; Moore, Jason H.

2011-01-01

Pleiotropy, in which one mutation causes multiple phenotypes, has traditionally been seen as a deviation from the conventional observation in which one gene affects one phenotype. Epistasis, or gene-gene interaction, has also been treated as an exception to the Mendelian one gene-one phenotype paradigm. This simplified perspective belies the pervasive complexity of biology and hinders progress toward a deeper understanding of biological systems. We assert that epistasis and pleiotropy are not isolated occurrences, but ubiquitous and inherent properties of biomolecular networks. These phenomena should not be treated as exceptions, but rather as fundamental components of genetic analyses. A systems level understanding of epistasis and pleiotropy is, therefore, critical to furthering our understanding of human genetics and its contribution to common human disease. Finally, graph theory offers an intuitive and powerful set of tools with which to study the network bases of these important genetic phenomena. PMID:19204994

Revisiting the NIH Taskforce on the Research needs of Eosinophil-Associated Diseases (RE-TREAD).

PubMed

Khoury, Paneez; Akuthota, Praveen; Ackerman, Steven J; Arron, Joseph R; Bochner, Bruce S; Collins, Margaret H; Kahn, Jean-Emmanuel; Fulkerson, Patricia C; Gleich, Gerald J; Gopal-Srivastava, Rashmi; Jacobsen, Elizabeth A; Leiferman, Kristen M; Francesca, Levi-Schaffer; Mathur, Sameer K; Minnicozzi, Michael; Prussin, Calman; Rothenberg, Marc E; Roufosse, Florence; Sable, Kathleen; Simon, Dagmar; Simon, Hans-Uwe; Spencer, Lisa A; Steinfeld, Jonathan; Wardlaw, Andrew J; Wechsler, Michael E; Weller, Peter F; Klion, Amy D

2018-04-19

Eosinophil-associated diseases (EADs) are rare, heterogeneous disorders characterized by the presence of eosinophils in tissues and/or peripheral blood resulting in immunopathology. The heterogeneity of tissue involvement, lack of sufficient animal models, technical challenges in working with eosinophils, and lack of standardized histopathologic approaches have hampered progress in basic research. Additionally, clinical trials and drug development for rare EADs are limited by the lack of primary and surrogate endpoints, biomarkers, and validated patient-reported outcomes. Researchers with expertise in eosinophil biology and eosinophil-related diseases reviewed the state of current eosinophil research, resources, progress, and unmet needs in the field since the 2012 meeting of the NIH Taskforce on the Research of Eosinophil-Associated Diseases (TREAD). RE-TREAD focused on gaps in basic science, translational, and clinical research on eosinophils and eosinophil-related pathogenesis. Improved recapitulation of human eosinophil biology and pathogenesis in murine models was felt to be of importance. Characterization of eosinophil phenotypes, the role of eosinophil subsets in tissues, identification of biomarkers of eosinophil activation and tissue load, and a better understanding of the role of eosinophils in human disease were prioritized. Finally, an unmet need for tools for use in clinical trials was emphasized. Histopathologic scoring, patient- and clinician-reported outcomes, and appropriate coding were deemed of paramount importance for research collaborations, drug development, and approval by regulatory agencies. Further exploration of the eosinophil genome, epigenome, and proteome was also encouraged. Although progress has been made since 2012, unmet needs in eosinophil research remain a priority. ©2018 Society for Leukocyte Biology.

Preclinical magnetic resonance imaging and systems biology in cancer research: current applications and challenges.

PubMed

Albanese, Chris; Rodriguez, Olga C; VanMeter, John; Fricke, Stanley T; Rood, Brian R; Lee, YiChien; Wang, Sean S; Madhavan, Subha; Gusev, Yuriy; Petricoin, Emanuel F; Wang, Yue

2013-02-01

Biologically accurate mouse models of human cancer have become important tools for the study of human disease. The anatomical location of various target organs, such as brain, pancreas, and prostate, makes determination of disease status difficult. Imaging modalities, such as magnetic resonance imaging, can greatly enhance diagnosis, and longitudinal imaging of tumor progression is an important source of experimental data. Even in models where the tumors arise in areas that permit visual determination of tumorigenesis, longitudinal anatomical and functional imaging can enhance the scope of studies by facilitating the assessment of biological alterations, (such as changes in angiogenesis, metabolism, cellular invasion) as well as tissue perfusion and diffusion. One of the challenges in preclinical imaging is the development of infrastructural platforms required for integrating in vivo imaging and therapeutic response data with ex vivo pathological and molecular data using a more systems-based multiscale modeling approach. Further challenges exist in integrating these data for computational modeling to better understand the pathobiology of cancer and to better affect its cure. We review the current applications of preclinical imaging and discuss the implications of applying functional imaging to visualize cancer progression and treatment. Finally, we provide new data from an ongoing preclinical drug study demonstrating how multiscale modeling can lead to a more comprehensive understanding of cancer biology and therapy. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A biotherapy based on PSCs-in-3D spheroid-ameliorated biologics depletes in vivo cancer-sustaining stem cells

PubMed Central

Zhou, Tianlin; Li, Meng; Wen, Yanjun; Lin, Xiaojuan; Xiang, Rong; Chen, Xiancheng

2015-01-01

CSCs are able to survive routine anticancer procedures and peripheral-immune attack. Here we develop and detail a framework of CSC elimination governed by 3D-biologics. Pluripotent cells-engineered 3D-biologics (PMSB) and control non-3D-biologics were prepared from placenta-based somatic stem cells (PSCs) and inoculated respectively into senile hosts bearing progressive mammary, lung, colon carcinomas and melanoma. We demonstrate that PMSB evokes in vivo central-immune microenvironment with subsequent re-expression of thymosin-α1 ~ β4 in thymic cortex-medulla borderline for rapid MHC-unrestricted renewal of γδT-dominated immunocompetence. The post-renewal γδT-subsets could accurately bind and drive CSCs into apoptosis. Finally, with central/peripheral integral microenvironment renewal and TERT/Wnt/β-catenin pathway blockade, the CSC-subsets are fully depleted, leading to substantial cure of diverse tumors by PMSB inoculation (P < 0.01), yet not by non-3D-biologics. Thus, our study may contribute to open up a new avenue for tumor remission via pluripotent cells-engineered 3D-biologics addressing quick renewal of central-thymus and peripheral immune-microenvironment. PMID:26512920

Recent Progress in Bionic Condensate Microdrop Self-Propelling Surfaces.

PubMed

Gong, Xiaojing; Gao, Xuefeng; Jiang, Lei

2017-12-01

Bionic condensate microdrop self-propelling (CMDSP) surfaces are attracting increased attention as novel, low-adhesivity superhydrophobic surfaces due to their value in fundamental research and technological innovation, e.g., for enhancing heat transfer, energy-effective antifreezing, and electrostatic energy harvesting. Here, the focus is on recent progress in bionic CMDSP surfaces. Metal-based CMDSP surfaces, which are the most promising in their respective fields, are highlighted for use in future applications. The selected topics are divided into four sections: biological prototypes, mechanism and construction rules, fabrication, and applications of metal-based CMDSP surfaces. Finally, the challenges and future development trends in bionic CMDSP surfaces are envisioned, especially the utilization of potential bionic inspiration in the design of more advanced CMDSP surfaces. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lipidomics in vascular health: current perspectives.

PubMed

Kolovou, Genovefa; Kolovou, Vana; Mavrogeni, Sophie

2015-01-01

Identifying the mechanisms that convert a healthy vascular wall to an atherosclerotic wall is of major importance since the consequences may lead to a shortened lifespan. Classical risk factors (age, smoking, obesity, diabetes mellitus, hypertension, and dyslipidemia) may result in the progression of atherosclerotic lesions by processes including inflammation and lipid accumulation. Thus, the evaluation of blood lipids and the full lipid complement produced by cells, organisms, or tissues (lipidomics) is an issue of importance. In this review, we shall describe the recent progress in vascular health research using lipidomic advances. We will begin with an overview of vascular wall biology and lipids, followed by a short analysis of lipidomics. Finally, we shall focus on the clinical implications of lipidomics and studies that have examined lipidomic approaches and vascular health.

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

Teaching Students How to Study: A Workshop on Information Processing and Self-Testing Helps Students Learn

PubMed Central

Stanger-Hall, Kathrin F.; Shockley, Floyd W.; Wilson, Rachel E.

2011-01-01

We implemented a “how to study” workshop for small groups of students (6–12) for N = 93 consenting students, randomly assigned from a large introductory biology class. The goal of this workshop was to teach students self-regulating techniques with visualization-based exercises as a foundation for learning and critical thinking in two areas: information processing and self-testing. During the workshop, students worked individually or in groups and received immediate feedback on their progress. Here, we describe two individual workshop exercises, report their immediate results, describe students’ reactions (based on the workshop instructors’ experience and student feedback), and report student performance on workshop-related questions on the final exam. Students rated the workshop activities highly and performed significantly better on workshop-related final exam questions than the control groups. This was the case for both lower- and higher-order thinking questions. Student achievement (i.e., grade point average) was significantly correlated with overall final exam performance but not with workshop outcomes. This long-term (10 wk) retention of a self-testing effect across question levels and student achievement is a promising endorsement for future large-scale implementation and further evaluation of this “how to study” workshop as a study support for introductory biology (and other science) students. PMID:21633067

[Research advances of fluid bio-mechanics in bone].

PubMed

Chen, Zebin; Huo, Bo

2017-04-01

It has been found for more than one century that when experiencing mechanical loading, the structure of bone will adapt to the changing mechanical environment, which is called bone remodeling. Bone remodeling is charaterized as two processes of bone formation and bone resorption. A large number of studies have confirmed that the shear stress is resulted from interstitial fluid flow within bone cavities under mechanical loading and it is the key factor of stimulating the biological responses of bone cells. This review summarizes the major research progress during the past years, including the biological response of bone cells under fluid flow, the pressure within bone cavities, the theoretical modeling, numerical simulation and experiments about fluid flow within bone, and finally analyzes and predicts the possible tendency in this field in the future.

Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and its Application in Life Sciences

NASA Astrophysics Data System (ADS)

Xu, Gu-feng; Wang, Hong-mei

2001-08-01

Inductively-coupled plasma mass spectrometry (ICP-MS) has made much progress since its birth in the late 1990s. This paper will give a rather systematic overview on the use of this technique in new devices and technologies related to plasma source, sample-introducing device and detecting spectrometer etc. In this overview, an emphasis will be put on the evaluation of the ICP-MS technique in combination with a series of physical, chemical and biological techniques, such as laser ablation (LA), capillary electrophoresis (CE) and high performance liquid chromatograph (HPLC), along with their representative high accuracy and high sensitivity. Finally, comprehensive and fruitful applications of the ICP-MS and its combinative techniques in the detection of trace metallic elements and isotopes in complex biological and environmental samples will be revealed.

Synthesis, Biological Evaluation, and Structure–Activity Relationships of Novel Substituted N-Phenyl Ureidobenzenesulfonate Derivatives Blocking Cell Cycle Progression in S-Phase and Inducing DNA Double-Strand Breaks

PubMed Central

2012-01-01

Twenty-eight new substituted N-phenyl ureidobenzenesulfonate (PUB-SO) and 18 N-phenylureidobenzenesulfonamide (PUB-SA) derivatives were prepared. Several PUB-SOs exhibited antiproliferative activity at the micromolar level against the HT-29, M21, and MCF-7 cell lines and blocked cell cycle progression in S-phase similarly to cisplatin. In addition, PUB-SOs induced histone H2AX (γH2AX) phosphorylation, indicating that these molecules induce DNA double-strand breaks. In contrast, PUB-SAs were less active than PUB-SOs and did not block cell cycle progression in S-phase. Finally, PUB-SOs 4 and 46 exhibited potent antitumor activity in HT-1080 fibrosarcoma cells grafted onto chick chorioallantoic membranes, which was similar to cisplatin and combretastatin A-4 and without significant toxicity toward chick embryos. These new compounds are members of a promising new class of anticancer agents. PMID:22694057

Synthesis, biological evaluation, and structure-activity relationships of novel substituted N-phenyl ureidobenzenesulfonate derivatives blocking cell cycle progression in S-phase and inducing DNA double-strand breaks.

PubMed

Turcotte, Vanessa; Fortin, Sébastien; Vevey, Florence; Coulombe, Yan; Lacroix, Jacques; Côté, Marie-France; Masson, Jean-Yves; C-Gaudreault, René

2012-07-12

Twenty-eight new substituted N-phenyl ureidobenzenesulfonate (PUB-SO) and 18 N-phenylureidobenzenesulfonamide (PUB-SA) derivatives were prepared. Several PUB-SOs exhibited antiproliferative activity at the micromolar level against the HT-29, M21, and MCF-7 cell lines and blocked cell cycle progression in S-phase similarly to cisplatin. In addition, PUB-SOs induced histone H2AX (γH2AX) phosphorylation, indicating that these molecules induce DNA double-strand breaks. In contrast, PUB-SAs were less active than PUB-SOs and did not block cell cycle progression in S-phase. Finally, PUB-SOs 4 and 46 exhibited potent antitumor activity in HT-1080 fibrosarcoma cells grafted onto chick chorioallantoic membranes, which was similar to cisplatin and combretastatin A-4 and without significant toxicity toward chick embryos. These new compounds are members of a promising new class of anticancer agents.

Fetal Alcohol Syndrome, Chemo-Biology and OMICS: Ethanol Effects on Vitamin Metabolism During Neurodevelopment as Measured by Systems Biology Analysis

PubMed Central

Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães

2014-01-01

Abstract Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment. PMID:24816220

Fetal alcohol syndrome, chemo-biology and OMICS: ethanol effects on vitamin metabolism during neurodevelopment as measured by systems biology analysis.

PubMed

Feltes, Bruno César; de Faria Poloni, Joice; Nunes, Itamar José Guimarães; Bonatto, Diego

2014-06-01

Fetal alcohol syndrome (FAS) is a prenatal disease characterized by fetal morphological and neurological abnormalities originating from exposure to alcohol. Although FAS is a well-described pathology, the molecular mechanisms underlying its progression are virtually unknown. Moreover, alcohol abuse can affect vitamin metabolism and absorption, although how alcohol impairs such biochemical pathways remains to be elucidated. We employed a variety of systems chemo-biology tools to understand the interplay between ethanol metabolism and vitamins during mouse neurodevelopment. For this purpose, we designed interactomes and employed transcriptomic data analysis approaches to study the neural tissue of Mus musculus exposed to ethanol prenatally and postnatally, simulating conditions that could lead to FAS development at different life stages. Our results showed that FAS can promote early changes in neurotransmitter release and glutamate equilibrium, as well as an abnormal calcium influx that can lead to neuroinflammation and impaired neurodifferentiation, both extensively connected with vitamin action and metabolism. Genes related to retinoic acid, niacin, vitamin D, and folate metabolism were underexpressed during neurodevelopment and appear to contribute to neuroinflammation progression and impaired synapsis. Our results also indicate that genes coding for tubulin, tubulin-associated proteins, synapse plasticity proteins, and proteins related to neurodifferentiation are extensively affected by ethanol exposure. Finally, we developed a molecular model of how ethanol can affect vitamin metabolism and impair neurodevelopment.

The History of Ecoimmunology and Its Integration with Disease Ecology

PubMed Central

Brock, Patrick M.; Murdock, Courtney C.; Martin, Lynn B.

2014-01-01

Ecoimmunology is an example of how fruitful integrative approaches to biology can be. Since its emergence, ecoimmunology has sparked constructive debate on a wide range of topics, from the molecular mechanics of immune responses to the role of immunity in shaping the evolution of life histories. To complement the symposium Methods and Mechanisms in Ecoimmunology and commemorate the inception of the Division of Ecoimmunology and Disease Ecology within the Society for Integrative and Comparative Biology, we appraise the origins of ecoimmunology, with a focus on its continuing and valuable integration with disease ecology. Arguably, the greatest contribution of ecoimmunology to wider biology has been the establishment of immunity as an integral part of organismal biology, one that may be regulated to maximize fitness in the context of costs, constraints, and complex interactions. We discuss historical impediments and ongoing progress in ecoimmunology, in particular the thorny issue of what ecoimmunologists should, should not, or cannot measure, and what novel contributions ecoimmunologists have made to the understanding of host–parasite interactions. Finally, we highlight some areas to which ecoimmunology is likely to contribute in the near future. PMID:24838746

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

Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Synthetic Biology Research Program, National University of Singapore, Singapore

Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fattymore » acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes.« less

The dual role of tumor necrosis factor (TNF) in cancer biology.

PubMed

Bertazza, Loris; Mocellin, Simone

2010-01-01

Tumor necrosis factor (TNF) is a cytokine with well known anticancer properties and is being utilized as anticancer agent for the treatment of patients with locally advanced solid tumors. However, TNF role in cancer biology is debated. In fact, in spite of the wealth of evidence supporting its antitumor activity, the cascade of molecular events underlying TNF-mediated tumor regression observed in vivo is still incompletely elucidated. Furthermore, some preclinical findings suggest that TNF may even promote cancer development and progression. With this work we intend to summarize the molecular biology of TNF (with particular regard to its tumor-related activities) and review the experimental and clinical evidence currently available describing the complex and sometime apparently conflicting relationship between this cytokine, cancer biology and antitumor therapy. We also propose a model to explain the dual effect of TNF based on the exposure time and cytokine levels reached within the tumor microenvironment. Finally, we overview recent research findings that might lead to new ways for exploiting the anticancer potential of TNF in the clinical setting.

Production of Fatty Acid-Derived Valuable Chemicals in Synthetic Microbes

PubMed Central

Yu, Ai-Qun; Pratomo Juwono, Nina Kurniasih; Leong, Susanna Su Jan; Chang, Matthew Wook

2014-01-01

Fatty acid derivatives, such as hydroxy fatty acids, fatty alcohols, fatty acid methyl/ethyl esters, and fatty alka(e)nes, have a wide range of industrial applications including plastics, lubricants, and fuels. Currently, these chemicals are obtained mainly through chemical synthesis, which is complex and costly, and their availability from natural biological sources is extremely limited. Metabolic engineering of microorganisms has provided a platform for effective production of these valuable biochemicals. Notably, synthetic biology-based metabolic engineering strategies have been extensively applied to refactor microorganisms for improved biochemical production. Here, we reviewed: (i) the current status of metabolic engineering of microbes that produce fatty acid-derived valuable chemicals, and (ii) the recent progress of synthetic biology approaches that assist metabolic engineering, such as mRNA secondary structure engineering, sensor-regulator system, regulatable expression system, ultrasensitive input/output control system, and computer science-based design of complex gene circuits. Furthermore, key challenges and strategies were discussed. Finally, we concluded that synthetic biology provides useful metabolic engineering strategies for economically viable production of fatty acid-derived valuable chemicals in engineered microbes. PMID:25566540

A discussion group program enhances the conceptual reasoning skills of students enrolled in a large lecture-format introductory biology course.

PubMed

Peteroy-Kelly, Marcy A

2007-01-01

It has been well-established that discussion groups enhance student learning in large lecture courses. The goal of this study was to determine the impact of a discussion group program on the development of conceptual reasoning skills of students enrolled in a large lecture-format introductory biology course. In the discussion group, students worked on problems based on topics discussed in lecture. The program was evaluated using three assessment tools. First, student responses to pre- and posttests were analyzed. The test question asked the students to demonstrate the relationships between 10 different but related terms. Use of a concept map to link the terms indicated an advanced level of conceptual reasoning skills. There was a 13.8% increase in the use of concept maps from pre- to posttest. Second, the students took a Likert-type survey to determine the perceived impact of the program on their conceptual reasoning skills. Many of the students felt that the program helped them understand and use the main course concepts to logically solve problems. Finally, average exam grades increased as the semester progressed. The average final grade in the course was 75%. Students enrolled in the course the previous year (where the lecture component of the course did not assess or reflect student learning in the discussion group) had an average final grade of 69%. The results of this study demonstrate that the discussion group program improves the conceptual reasoning skills of students enrolled in a large lecture-format introductory biology course.

High-strength wastewater treatment in a pure oxygen thermophilic process: 11-year operation and monitoring of different plant configurations.

PubMed

Collivignarelli, M C; Bertanza, G; Sordi, M; Pedrazzani, R

2015-01-01

This research was carried out on a full-scale pure oxygen thermophilic plant, operated and monitored throughout a period of 11 years. The plant treats 60,000 t y⁻¹ (year 2013) of high-strength industrial wastewaters deriving mainly from pharmaceuticals and detergents production and landfill leachate. Three different plant configurations were consecutively adopted: (1) biological reactor + final clarifier and sludge recirculation (2002-2005); (2) biological reactor + ultrafiltration: membrane biological reactor (MBR) (2006); and (3) MBR + nanofiltration (since 2007). Progressive plant upgrading yielded a performance improvement chemical oxygen demand (COD) removal efficiency was enhanced by 17% and 12% after the first and second plant modification, respectively. Moreover, COD abatement efficiency exhibited a greater stability, notwithstanding high variability of the influent load. In addition, the following relevant outcomes appeared from the plant monitoring (present configuration): up to 96% removal of nitrate and nitrite, due to denitrification; low-specific biomass production (0.092 kgVSS kgCODremoved⁻¹), and biological treatability of residual COD under mesophilic conditions (BOD5/COD ratio = 0.25-0.50), thus showing the complementarity of the two biological processes.

[Specificities of the logopenic variant of primary progressive aphasia].

PubMed

Magnin, E; Teichmann, M; Martinaud, O; Moreaud, O; Ryff, I; Belliard, S; Pariente, J; Moulin, T; Vandel, P; Démonet, J-F

2015-01-01

The logopenic variant of primary progressive aphasia is a syndrome with neuropsychological and linguistic specificities, including phonological loop impairment for which diagnosis is currently mainly based on the exclusion of the two other variants, semantic and nonfluent/agrammatic primary progressive aphasia. The syndrome may be underdiagnosed due (1) to mild language difficulties during the early stages of the disease or (2) to being mistaken for mild cognitive impairment or Alzheimer's disease when the evaluation of episodic memory is based on verbal material and (3) finally, it is not uncommon that the disorders are attributed to psychiatric co-morbidities such as, for example, anxiety. Moreover, compared to other variants of primary progressive aphasia, brain abnormalities are different. The left temporoparietal junction is initially affected. Neuropathology and biomarkers (cerebrospinal fluid, molecular amyloid nuclear imaging) frequently reveal Alzheimer's disease. Consequently this variant of primary progressive aphasia does not fall under the traditional concept of frontotemporal lobar degeneration. These distinctive features highlight the utility of correct diagnosis, classification, and use of biomarkers to show the neuropathological processes underlying logopenic primary progressive aphasia. The logopenic variant of primary progressive aphasia is a specific form of Alzheimer's disease frequently presenting a rapid decline; specific linguistic therapies are needed. Further investigation of this syndrome is needed to refine screening, improve diagnostic criteria and better understand the epidemiology and the biological mechanisms involved. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Progress in synthetic biology of "973 Funding Program" in China].

PubMed

Chen, Guoqiang; Wang, Ying

2015-06-01

This paper reviews progresses made in China from 2011 in areas of "Synthetic Biology" supported by State Basic Research 973 Program. Till the end of 2014, 9 "synthetic biology" projects have been initiated with emphasis on "microbial manufactures" with the 973 Funding Program. Combined with the very recent launch of one project on "mammalian cell synthetic biology" and another on "plant synthetic biology", Chinese "synthetic biology" research reflects its focus on "manufactures" while not giving up efforts on "synthetic biology" of complex systems.

Energy resource alternatives competition. Progress report for the period February 1, 1975--December 31, 1975. [Space heating and cooling, hot water, and electricity for homes, farms, and light industry

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

Matzke, D.J.; Osowski, D.M.; Radtke, M.L.

1976-01-01

This progress report describes the objectives and results of the intercollegiate Energy Resource Alternatives competition. The one-year program concluded in August 1975, with a final testing program of forty student-built alternative energy projects at the Sandia Laboratories in Albuquerque, New Mexico. The goal of the competition was to design and build prototype hardware which could provide space heating and cooling, hot water, and electricity at a level appropriate to the needs of homes, farms, and light industry. The hardware projects were powered by such nonconventional energy sources as solar energy, wind, biologically produced gas, coal, and ocean waves. The competitionmore » rules emphasized design innovation, economic feasibility, practicality, and marketability. (auth)« less

Genomics, transcriptomics and proteomics: enabling insights into social evolution and disease challenges for managed and wild bees.

PubMed

Trapp, Judith; McAfee, Alison; Foster, Leonard J

2017-02-01

Globally, there are over 20 000 bee species (Hymenoptera: Apoidea: Anthophila) with a host of biologically fascinating characteristics. Although they have long been studied as models for social evolution, recent challenges to bee health (mainly diseases and pesticides) have gathered the attention of both public and research communities. Genome sequences of twelve bee species are now complete or under progress, facilitating the application of additional 'omic technologies. Here, we review recent developments in honey bee and native bee research in the genomic era. We discuss the progress in genome sequencing and functional annotation, followed by the enabled comparative genomics, proteomics and transcriptomics applications regarding social evolution and health. Finally, we end with comments on future challenges in the postgenomic era. © 2016 John Wiley & Sons Ltd.

A review on PARP1 inhibitors: Pharmacophore modeling, virtual and biological screening studies to identify novel PARP1 inhibitors.

PubMed

Singh, Sardar Shamshair; Sarma, Jagarlapudi A R P; Narasu, Lakshmi; Dayam, Raveendra; Xu, Shili; Neamati, Nouri

2014-01-01

A tremendous research on Poly (ADP-ribose) polymerase (PARP) pertaining to cancer and ischemia is in very rapid progress. PARP's are a specific class of enzymes that repairs the damaged DNA. Recent findings suggest also that PARP-1 is the most abundantly expressed nuclear enzyme which involves in various therapeutic areas like inflammation, stroke, cardiac ischemia, cancer and diabetes. The current review describes the overview on clinical candidates of PARP1 and its current status in clinical trials. This paper also covers identification of potent PARP1 inhibitors using structure and ligand based pharmacophore models. Finally 36 potential hits were identified from the virtual screening of pharmacophore models and screened for PARP1 activity. 15 actives were identified as potent PARP1 inhibitors and further optimization of these analogues are in progress.

New perspectives in toxicological information management, and the role of ISSTOX databases in assessing chemical mutagenicity and carcinogenicity.

PubMed

Benigni, Romualdo; Battistelli, Chiara Laura; Bossa, Cecilia; Tcheremenskaia, Olga; Crettaz, Pierre

2013-07-01

Currently, the public has access to a variety of databases containing mutagenicity and carcinogenicity data. These resources are crucial for the toxicologists and regulators involved in the risk assessment of chemicals, which necessitates access to all the relevant literature, and the capability to search across toxicity databases using both biological and chemical criteria. Towards the larger goal of screening chemicals for a wide range of toxicity end points of potential interest, publicly available resources across a large spectrum of biological and chemical data space must be effectively harnessed with current and evolving information technologies (i.e. systematised, integrated and mined), if long-term screening and prediction objectives are to be achieved. A key to rapid progress in the field of chemical toxicity databases is that of combining information technology with the chemical structure as identifier of the molecules. This permits an enormous range of operations (e.g. retrieving chemicals or chemical classes, describing the content of databases, finding similar chemicals, crossing biological and chemical interrogations, etc.) that other more classical databases cannot allow. This article describes the progress in the technology of toxicity databases, including the concepts of Chemical Relational Database and Toxicological Standardized Controlled Vocabularies (Ontology). Then it describes the ISSTOX cluster of toxicological databases at the Istituto Superiore di Sanitá. It consists of freely available databases characterised by the use of modern information technologies and by curation of the quality of the biological data. Finally, this article provides examples of analyses and results made possible by ISSTOX.

Function and Biosynthesis of Cell Wall α-1,3-Glucan in Fungi.

PubMed

Yoshimi, Akira; Miyazawa, Ken; Abe, Keietsu

2017-11-18

Although α-1,3-glucan is a major cell wall polysaccharide in filamentous fungi, its biological functions remain unclear, except that it acts as a virulence factor in animal and plant pathogenic fungi: it conceals cell wall β-glucan on the fungal cell surface to circumvent recognition by hosts. However, cell wall α-1,3-glucan is also present in many of non-pathogenic fungi. Recently, the universal function of α-1,3-glucan as an aggregation factor has been demonstrated. Applications of fungi with modified cell wall α-1,3-glucan in the fermentation industry and of in vitro enzymatically-synthesized α-1,3-glucan in bio-plastics have been developed. This review focuses on the recent progress in our understanding of the biological functions and biosynthetic mechanism of cell wall α-1,3-glucan in fungi. We briefly consider the history of studies on α-1,3-glucan, overview its biological functions and biosynthesis, and finally consider the industrial applications of fungi deficient in α-1,3-glucan.

Pine Gene Discovery Project - Final Report - 08/31/1997 - 02/28/2001

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

Whetten, R. W.; Sederoff, R. R.; Kinlaw, C.

2001-04-30

Integration of pines into the large scope of plant biology research depends on study of pines in parallel with study of annual plants, and on availability of research materials from pine to plant biologists interested in comparing pine with annual plant systems. The objectives of the Pine Gene Discovery Project were to obtain 10,000 partial DNA sequences of genes expressed in loblolly pine, to determine which of those pine genes were similar to known genes from other organisms, and to make the DNA sequences and isolated pine genes available to plant researchers to stimulate integration of pines into the widermore » scope of plant biology research. Those objectives have been completed, and the results are available to the public. Requests for pine genes have been received from a number of laboratories that would otherwise not have included pine in their research, indicating that progress is being made toward the goal of integrating pine research into the larger molecular biology research community.« less

Intersections of lung progenitor cells, lung disease and lung cancer.

PubMed

Kim, Carla F

2017-06-30

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

A Biobehavioral Model of Cancer Stress and Disease Course

PubMed Central

Andersen, Barbara L.; Kiecolt-Glaser, Janice K.; Glaser, Ronald

2009-01-01

Approximately 1 million Americans are diagnosed with cancer each year and must cope with the disease and treatments. Many studies have documented the deteriorations in quality of life that occur. These data suggest that the adjustment process is burdensome and lengthy. There is ample evidence showing that adults experiencing other long-term stressors experience not only high rates of adjustment difficulties (e.g., syndromal depression) but important biologic effects, such as persistent downregulation of elements of the immune system, and adverse health outcomes, such as higher rates of respiratory tract infections. Thus, deteriorations in quality of life with cancer are underscored if they have implications for biological processes, such as the immune system, relating to disease progression and spread. Considering these and other data, a biobehavioral model of adjustment to the stresses of cancer is offered, and mechanisms by which psychological and behavioral responses may influence biological processes and, perhaps, health outcomes are proposed. Finally, strategies for testing the model via experiments testing psychological interventions are offered. PMID:8024167

Concise Review: Mending a Broken Heart: The Evolution of Biological Therapeutics.

PubMed

Chen, Caressa; Termglinchan, Vittavat; Karakikes, Ioannis

2017-05-01

Heart failure (HF), a common sequela of cardiovascular diseases, remains a staggering clinical problem, associated with high rates of morbidity and mortality worldwide. Advances in pharmacological, interventional, and operative management have improved patient care, but these interventions are insufficient to halt the progression of HF, particularly the end-stage irreversible loss of functional cardiomyocytes. Innovative therapies that could prevent HF progression and improve the function of the failing heart are urgently needed. Following successful preclinical studies, two main strategies have emerged as potential solutions: cardiac gene therapy and cardiac regeneration through stem and precursor cell transplantation. Many potential gene- and cell-based therapies have entered into clinical studies, intending to ameliorate cardiac dysfunction in patients with advanced HF. In this review, we focus on the recent advances in cell- and gene-based therapies in the context of cardiovascular disease, emphasizing the most advanced therapies. The principles and mechanisms of action of gene and cell therapies for HF are discussed along with the limitations of current approaches. Finally, we highlight the emerging technologies that hold promise to revolutionize the biological therapies for cardiovascular diseases. Stem Cells 2017;35:1131-1140. © 2017 AlphaMed Press.

Physical break-down of the classical view on cancer cell invasion and metastasis.

PubMed

Mierke, Claudia T

2013-03-01

Eight classical hallmarks of cancer have been proposed and are well-defined by using biochemical or molecular genetic methods, but are not yet precisely defined by cellular biophysical processes. To define the malignant transformation of neoplasms and finally reveal the functional pathway, which enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific biomechanical properties of cancer cells and their microenvironment such as the extracellular matrix and embedded cells such as fibroblasts, macrophages or endothelial cells. Nonetheless a main novel ninth hallmark of cancer is still elusive in classical tumor biological reviews, which is the aspect of physics in cancer disease by the natural selection of an aggressive (highly invasive) subtype of cancer cells. The physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present current cancer research in a different light and will focus on novel physical methods to investigate the aggressiveness of cancer cells from a biophysicist's point of view. This may lead to novel insights into cancer disease and will overcome classical views on cancer. In addition, this review will discuss how physics of cancer can help to reveal whether cancer cells will invade connective tissue and metastasize. In particular, this review will point out how physics can improve, break-down or support classical approaches to examine tumor growth even across primary tumor boundaries, the invasion of single or collective cancer cells, transendothelial migration of cancer cells and metastasis in targeted organs. Finally, this review will show how physical measurements can be integrated into classical tumor biological analysis approaches. The insights into physical interactions between cancer cells, the primary tumor and the microenvironment may help to solve some "old" questions in cancer disease progression and may finally lead to novel approaches for development and improvement of cancer diagnostics and therapies. Copyright © 2013 Elsevier GmbH. All rights reserved.

On disciplinary fragmentation and scientific progress.

PubMed

Balietti, Stefano; Mäs, Michael; Helbing, Dirk

2015-01-01

Why are some scientific disciplines, such as sociology and psychology, more fragmented into conflicting schools of thought than other fields, such as physics and biology? Furthermore, why does high fragmentation tend to coincide with limited scientific progress? We analyzed a formal model where scientists seek to identify the correct answer to a research question. Each scientist is influenced by three forces: (i) signals received from the correct answer to the question; (ii) peer influence; and (iii) noise. We observed the emergence of different macroscopic patterns of collective exploration, and studied how the three forces affect the degree to which disciplines fall apart into divergent fragments, or so-called "schools of thought". We conducted two simulation experiments where we tested (A) whether the three forces foster or hamper progress, and (B) whether disciplinary fragmentation causally affects scientific progress and vice versa. We found that fragmentation critically limits scientific progress. Strikingly, there is no effect in the opposite causal direction. What is more, our results shows that at the heart of the mechanisms driving scientific progress we find (i) social interactions, and (ii) peer disagreement. In fact, fragmentation is increased and progress limited if the simulated scientists are open to influence only by peers with very similar views, or when within-school diversity is lost. Finally, disciplines where the scientists received strong signals from the correct answer were less fragmented and experienced faster progress. We discuss model's implications for the design of social institutions fostering interdisciplinarity and participation in science.

On Disciplinary Fragmentation and Scientific Progress

PubMed Central

Balietti, Stefano; Mäs, Michael; Helbing, Dirk

2015-01-01

Why are some scientific disciplines, such as sociology and psychology, more fragmented into conflicting schools of thought than other fields, such as physics and biology? Furthermore, why does high fragmentation tend to coincide with limited scientific progress? We analyzed a formal model where scientists seek to identify the correct answer to a research question. Each scientist is influenced by three forces: (i) signals received from the correct answer to the question; (ii) peer influence; and (iii) noise. We observed the emergence of different macroscopic patterns of collective exploration, and studied how the three forces affect the degree to which disciplines fall apart into divergent fragments, or so-called “schools of thought”. We conducted two simulation experiments where we tested (A) whether the three forces foster or hamper progress, and (B) whether disciplinary fragmentation causally affects scientific progress and vice versa. We found that fragmentation critically limits scientific progress. Strikingly, there is no effect in the opposite causal direction. What is more, our results shows that at the heart of the mechanisms driving scientific progress we find (i) social interactions, and (ii) peer disagreement. In fact, fragmentation is increased and progress limited if the simulated scientists are open to influence only by peers with very similar views, or when within-school diversity is lost. Finally, disciplines where the scientists received strong signals from the correct answer were less fragmented and experienced faster progress. We discuss model’s implications for the design of social institutions fostering interdisciplinarity and participation in science. PMID:25790025

The Recent Developments in Sample Preparation for Mass Spectrometry-Based Metabolomics.

PubMed

Gong, Zhi-Gang; Hu, Jing; Wu, Xi; Xu, Yong-Jiang

2017-07-04

Metabolomics is a critical member in systems biology. Although great progress has been achieved in metabolomics, there are still some problems in sample preparation, data processing and data interpretation. In this review, we intend to explore the roles, challenges and trends in sample preparation for mass spectrometry- (MS-) based metabolomics. The newly emerged sample preparation methods were also critically examined, including laser microdissection, in vivo sampling, dried blood spot, microwave, ultrasound and enzyme-assisted extraction, as well as microextraction techniques. Finally, we provide some conclusions and perspectives for sample preparation in MS-based metabolomics.

[Research progress on real-time deformable models of soft tissues for surgery simulation].

PubMed

Xu, Shaoping; Liu, Xiaoping; Zhang, Hua; Luo, Jie

2010-04-01

Biological tissues generally exhibit nonlinearity, anisotropy, quasi-incompressibility and viscoelasticity about material properties. Simulating the behaviour of elastic objects in real time is one of the current objectives of virtual surgery simulation which is still a challenge for researchers to accurately depict the behaviour of human tissues. In this paper, we present a classification of the different deformable models that have been developed. We present the advantages and disadvantages of each one. Finally, we make a comparison of deformable models and perform an evaluation of the state of the art and the future of deformable models.

Programmable chemical reaction networks: emulating regulatory functions in living cells using a bottom-up approach.

PubMed

van Roekel, Hendrik W H; Rosier, Bas J H M; Meijer, Lenny H H; Hilbers, Peter A J; Markvoort, Albert J; Huck, Wilhelm T S; de Greef, Tom F A

2015-11-07

Living cells are able to produce a wide variety of biological responses when subjected to biochemical stimuli. It has become apparent that these biological responses are regulated by complex chemical reaction networks (CRNs). Unravelling the function of these circuits is a key topic of both systems biology and synthetic biology. Recent progress at the interface of chemistry and biology together with the realisation that current experimental tools are insufficient to quantitatively understand the molecular logic of pathways inside living cells has triggered renewed interest in the bottom-up development of CRNs. This builds upon earlier work of physical chemists who extensively studied inorganic CRNs and showed how a system of chemical reactions can give rise to complex spatiotemporal responses such as oscillations and pattern formation. Using purified biochemical components, in vitro synthetic biologists have started to engineer simplified model systems with the goal of mimicking biological responses of intracellular circuits. Emulation and reconstruction of system-level properties of intracellular networks using simplified circuits are able to reveal key design principles and molecular programs that underlie the biological function of interest. In this Tutorial Review, we present an accessible overview of this emerging field starting with key studies on inorganic CRNs followed by a discussion of recent work involving purified biochemical components. Finally, we review recent work showing the versatility of programmable biochemical reaction networks (BRNs) in analytical and diagnostic applications.

LncRNA MEG3 repressed malignant melanoma progression via inactivating Wnt signaling pathway.

PubMed

Li, Peng; Gao, Ying; Li, Jun; Zhou, Yu; Yuan, Jing; Guan, Huiwen; Yao, Peng

2018-05-21

Accumulating evidence has indicated that MEG3 can serve as a tumor suppressive lncRNA in various tumors. It is aberrantly expressed in multiple cancers. However, the biological roles of MEG3 in melanoma are poorly understood. Therefore, in our study, we concentrated on the biological mechanism of MEG3 in melanoma progression. First, we observed that MEG3 was obviously decreased in melanoma cells including A375, SK-MEL-1, B16, and A2058 cells compared to human epidermal melanocytes HEMa-LP. MEG3 was restored by transfecting LV-MEG3 in to A375 and A2058 cells. Subsequently, we found that overexpression of MEG3 was able to inhibit cell proliferation and colony formation capacity. Meanwhile, melanoma cell apoptosis was induced by up-regulation of MEG3. Overexpression of MEG3 greatly repressed melanoma cell migration and invasion ability. In addition, Wnt signaling pathway has been identified in the progression of various cancers. Here, in our study, it was indicated that Wnt signaling was highly activated in melanoma cells with β-catenin expression significantly increased and GSK-3β decreased. Interestingly, MEG restoration strongly inactivated Wnt signaling pathway by reducing β-catenin and CyclinD1, elevating GSK-3β levels in vitro. Finally, in vivo experiments were carried out to confirm the inhibitory roles of MEG3 in vivo. Taken these together, we suggested that MEG3 can inhibit melanoma development through blocking Wnt signaling pathway. © 2018 Wiley Periodicals, Inc.

Understanding the intersections between metabolism and cancer biology

PubMed Central

Heiden, Matthew G. Vander; DeBerardinis, Ralph J.

2017-01-01

Transformed cells adapt metabolism to support tumor initiation and progression. Specific metabolic activities can participate directly in the process of transformation or support the biological processes that enable tumor growth. Exploiting cancer metabolism for clinical benefit requires defining the pathways that are limiting for cancer progression and understanding the context specificity of metabolic preferences and liabilities in malignant cells. Progress towards answering these questions is providing new insight into cancer biology and can guide the more effective targeting of metabolism to help patients. PMID:28187287

Long-term treatment of an addictive personality.

PubMed

Seymour, Peter M

2003-01-01

There is infrequent discussion of long-term psychotherapy of persons with addiction, particularly in the self-psychology literature. In addition, some question whether long-term psychotherapy can be helpful in severe psychiatric disorders. The author describes the treatment of a woman with multiple diagnoses, including bulimia and alcohol and drug addiction, which took place over a period of almost 7 years. These issues are addressed from a self-psychological perspective, with progression of the treatment from early facilitation of a selfobject transference to more intense selfobject transference-countertransference states. Behavioral interventions (e.g., recommendation of inpatient chemical dependency treatment) are also discussed. The author describes the patient's dramatic progress and subsequent regression. Finally, there is a discussion of the addiction from self-psychological and biological perspectives of this woman's particular developmental and treatment issues, as well as a discussion of the confrontation and limit setting in a self-psychologically oriented treatment.

Enrichment and separation techniques for large-scale proteomics analysis of the protein post-translational modifications.

PubMed

Huang, Junfeng; Wang, Fangjun; Ye, Mingliang; Zou, Hanfa

2014-11-06

Comprehensive analysis of the post-translational modifications (PTMs) on proteins at proteome level is crucial to elucidate the regulatory mechanisms of various biological processes. In the past decades, thanks to the development of specific PTM enrichment techniques and efficient multidimensional liquid chromatography (LC) separation strategy, the identification of protein PTMs have made tremendous progress. A huge number of modification sites for some major protein PTMs have been identified by proteomics analysis. In this review, we first introduced the recent progresses of PTM enrichment methods for the analysis of several major PTMs including phosphorylation, glycosylation, ubiquitination, acetylation, methylation, and oxidation/reduction status. We then briefly summarized the challenges for PTM enrichment. Finally, we introduced the fractionation and separation techniques for efficient separation of PTM peptides in large-scale PTM analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Epigenetics: A way to bridge the gap between biological fields.

PubMed

Nicoglou, Antonine; Merlin, Francesca

2017-12-01

The concept of epigenetics has evolved since Waddington defined it from the late 1930s as the study of the causal mechanisms at work in development. It has become a multi-faceted notion with different meanings, depending on the disciplinary context it is used. In this article, we first analyse the transformations of the concept of epigenetics, from Waddington to contemporary accounts, in order to identify its different meanings and traditions, and to come up with a typology of epigenetics throughout its history. Second, we show on this basis that epigenetics has progressively turned its main focus from biological problems regarding development, toward issues concerning evolution. Yet, both these different epistemological aspects of epigenetics still coexist. Third, we claim that the classical opposition between epigenesis and preformationism as ways of thinking about the developmental process is part of the history of epigenetics and has contributed to its current various meanings. With these objectives in mind, we first show how Waddington introduced the term "epigenetics" in a biological context in order to solve a developmental problem, and we then build on this by presenting Nanney's, Riggs' and Holliday's definitions, which form the basis for the current conception of "molecular epigenetics". Then, we show that the evo-devo research field is where some particular uses of epigenetics have started shifting from developmental issues to evolutionary problems. We also show that epigenetics has progressively focused on the issue of epigenetic inheritance within the Extended Evolutionary Synthesis' framework. Finally, we conclude by presenting a typology of the different conceptions of epigenetics throughout time, and analyse the connections between them. We argue that, since Waddington, epigenetics, as an integrative research area, has been used to bridge the gap between different biological fields. Copyright © 2017 Elsevier Ltd. All rights reserved.

Grant Closeout Requirements and Reports

Cancer.gov

Requirements and reports to comply with grant closeout, including Final Federal Financial Report (FFR, SF425); Final Research Performance Progress Report (FRPPR); Interim Research Performance Progress Report (IRPPR); Final Invention Statement (FIS, HHS

Statistical molecular design of balanced compound libraries for QSAR modeling.

PubMed

Linusson, A; Elofsson, M; Andersson, I E; Dahlgren, M K

2010-01-01

A fundamental step in preclinical drug development is the computation of quantitative structure-activity relationship (QSAR) models, i.e. models that link chemical features of compounds with activities towards a target macromolecule associated with the initiation or progression of a disease. QSAR models are computed by combining information on the physicochemical and structural features of a library of congeneric compounds, typically assembled from two or more building blocks, and biological data from one or more in vitro assays. Since the models provide information on features affecting the compounds' biological activity they can be used as guides for further optimization. However, in order for a QSAR model to be relevant to the targeted disease, and drug development in general, the compound library used must contain molecules with balanced variation of the features spanning the chemical space believed to be important for interaction with the biological target. In addition, the assays used must be robust and deliver high quality data that are directly related to the function of the biological target and the associated disease state. In this review, we discuss and exemplify the concept of statistical molecular design (SMD) in the selection of building blocks and final synthetic targets (i.e. compounds to synthesize) to generate information-rich, balanced libraries for biological testing and computation of QSAR models.

Zonal Articular Cartilage Possesses Complex Mechanical Behavior Spanning Multiple Length Scales: Dependence on Chemical Heterogeneity, Anisotropy, and Microstructure

NASA Astrophysics Data System (ADS)

Wahlquist, Joseph A.

This work focused on characterizing the mechanical behavior of biological material in physiologically relevant conditions and at sub millimeter length scales. Elucidating the time, length scale, and directionally dependent mechanical behavior of cartilage and other biological materials is critical to adequately recapitulate native mechanosensory cues for cells, create computational models that mimic native tissue behavior, and assess disease progression. This work focused on three broad aspects of characterizing the mechanical behavior of articular cartilage. First, we sought to reveal the causes of time-dependent deformation and variation of mechanical properties with distance from the articular surface. Second, we investigated size dependence of mechanical properties. Finally, we examined material anisotropy of both the calcified and uncalcified tissues of the osteochondral interface. This research provides insight into how articular cartilage serves to support physiologic loads and simultaneously sustain chondrocyte viability.

Biomechanical forces in the skeleton and their relevance to bone metastasis: biology and engineering considerations

PubMed Central

Lynch, Maureen; Fischbach, Claudia

2014-01-01

Bone metastasis represents the leading cause of breast cancer related-deaths. However, the effect of skeleton-associated biomechanical signals on the initiation, progression, and therapy response of breast cancer bone metastasis is largely unknown. This review seeks to highlight possible functional connections between skeletal mechanical signals and breast cancer bone metastasis and their contribution to clinical outcome. It provides an introduction to the physical and biological signals underlying bone functional adaptation and discusses the modulatory roles of mechanical loading and breast cancer metastasis in this process. Following a definition of biophysical design criteria, in vitro and in vivo approaches from the fields of bone biomechanics and tissue engineering will be reviewed that may be suitable to investigate breast cancer bone metastasis as a function of varied mechano-signaling. Finally, an outlook of future opportunities and challenges associated with this newly emerging field will be provided. PMID:25174311

Magnetic nanomaterials and sensors for biological detection.

PubMed

Sobczak-Kupiec, Agnieszka; Venkatesan, Jayachandran; Alhathal AlAnezi, Adnan; Walczyk, Dorota; Farooqi, Ammad; Malina, Dagmara; Hosseini, Seyed Hossein; Tyliszczak, Bozena

2016-11-01

It is becoming progressively more understandable that sensitivity and versatility of magnetic biosensors provides unique platform for high performance diagnostics in clinical settings. Confluence of information suggested that magnetic biosensors required well-tailored magnetic particles as probes for detection that generate large and specific biological signal with minimum possible nonspecific binding. However, there are visible knowledge gaps in our understanding of the strategies to overcome existing challenges related to even smaller size of intracellular targets and lower signal-to-noise ratio than that in whole-cell studies, therefore tool designing and development for intracellular measurement and manipulation is problematic. In this review we describe magnetic nanoparticles, synthesis and sensing principles of magnetic nanoparticles as well as surface functionalization and modification and finally magnetic nanoparticles for medical diagnostics. This review gathers important and up-to-date information and may help to develop the method of obtaining magnetic materials especially for medical application. Copyright © 2016 Elsevier Inc. All rights reserved.

Advances in translational research in neuro-oncology.

PubMed

Fueyo, Juan; Gomez-Manzano, Candelaria; Yung, W K Alfred

2011-03-01

During the last decade, we have witnessed several key advances in the field of neuro-oncology. First, there were conceptual advances in the molecular and cell biology of malignant gliomas including the discovery in 2004 of brain tumor stem cells. Second, the Cancer Genome Atlas project has been extremely useful in the discovery of new molecular markers, including mutations in the IDH1 gene, and has led to a new classification of gliomas based on the differentiation status and mesenchymal transformation. In addition, use of the 1p/19q marker and O6-methylguanine-DNA methyltransferase methylation status have been identified as guides for patient selection for therapies and represent the first steps toward personalized medicine for treating gliomas. Finally, progress has been made in treatment strategies including the establishment of temozolomide as the criterion standard for treating gliomas, the adoption of bevacizumab in the clinical setting, and developments in experimental biological therapies including cancer vaccines and oncolytic adenoviruses.

Integrating population genetics and conservation biology in the era of genomics.

PubMed

Ouborg, N Joop

2010-02-23

As one of the final activities of the ESF-CONGEN Networking programme, a conference entitled 'Integrating Population Genetics and Conservation Biology' was held at Trondheim, Norway, from 23 to 26 May 2009. Conference speakers and poster presenters gave a display of the state-of-the-art developments in the field of conservation genetics. Over the five-year running period of the successful ESF-CONGEN Networking programme, much progress has been made in theoretical approaches, basic research on inbreeding depression and other genetic processes associated with habitat fragmentation and conservation issues, and with applying principles of conservation genetics in the conservation of many species. Future perspectives were also discussed in the conference, and it was concluded that conservation genetics is evolving into conservation genomics, while at the same time basic and applied research on threatened species and populations from a population genetic point of view continues to be emphasized.

The recent development and applications of fluidic channels by 3D printing.

PubMed

Zhou, Yufeng

2017-10-18

The technology of "Lab-on-a-Chip" allows the synthesis and analysis of chemicals and biological substance within a portable or handheld device. The 3D printed structures enable precise control of various geometries. The combination of these two technologies in recent years makes a significant progress. The current approaches of 3D printing, such as stereolithography, polyjet, and fused deposition modeling, are introduced. Their manufacture specifications, such as surface roughness, resolution, replication fidelity, cost, and fabrication time, are compared with each other. Finally, novel application of 3D printed channel in biology are reviewed, including pathogenic bacteria detection using magnetic nanoparticle clusters in a helical microchannel, cell stimulation by 3D chemical gradients, perfused functional vascular channels, 3D tissue construct, organ-on-a-chip, and miniaturized fluidic "reactionware" devices for chemical syntheses. Overall, the 3D printed fluidic chip is becoming a powerful tool in the both medical and chemical industries.

Dearomative dihydroxylation with arenophiles

NASA Astrophysics Data System (ADS)

Southgate, Emma H.; Pospech, Jola; Fu, Junkai; Holycross, Daniel R.; Sarlah, David

2016-10-01

Aromatic hydrocarbons are some of the most elementary feedstock chemicals, produced annually on a million metric ton scale, and are used in the production of polymers, paints, agrochemicals and pharmaceuticals. Dearomatization reactions convert simple, readily available arenes into more complex molecules with broader potential utility, however, despite substantial progress and achievements in this field, there are relatively few methods for the dearomatization of simple arenes that also selectively introduce functionality. Here we describe a new dearomatization process that involves visible-light activation of small heteroatom-containing organic molecules—arenophiles—that results in their para-cycloaddition with a variety of aromatic compounds. The approach uses N-N-arenophiles to enable dearomative dihydroxylation and diaminodihydroxylation of simple arenes. This strategy provides direct and selective access to highly functionalized cyclohexenes and cyclohexadienes and is orthogonal to existing chemical and biological dearomatization processes. Finally, we demonstrate the synthetic utility of this strategy with the concise synthesis of several biologically active compounds and natural products.

RNA Characterization by Solid-State NMR Spectroscopy.

PubMed

Yang, Yufei; Wang, Shenlin

2018-06-21

The structures of RNAs, which play critical roles in various biological processes, provide important clues and insights into the biological functions of these molecules. However, RNA structure determination remains a challenging topic. In recent years, magic-angle-spinning solid-state NMR (MAS SSNMR) has emerged as an alternative technique for structural and dynamic characterization of RNA. MAS SSNMR has been successfully applied to provide atomic-level structural information about several RNA molecules and RNA-protein complexes. In this Minireview, we give an overview of recent progress in the field of MAS SSNMR based RNA structural characterization, and introduce sample preparation strategies and SSNMR spectroscopic techniques that have been incorporated to identify RNA structural elements. We also highlight a few impressive examples of RNAs that have been investigated extensively by SSNMR. Finally, we briefly discuss future technical trends in the use of MAS SSNMR to facilitate RNA structure determination. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

NASA Astrophysics Data System (ADS)

Mierke, Claudia T.

There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present current cancer research in a different light from a physical point of view with respect to cancer cell mechanics and the special and unique role of the endothelium on cancer cell invasion. The physical view on cancer disease may lead to novel insights into cancer disease and will help to overcome the classical views on cancer. In addition, in this review it will be discussed how physics of cancer can help to reveal and propose the functional mechanism which cancer cells use to invade connective tissue and transmigrate through the endothelium to finally metastasize. Finally, in this review it will be demonstrated how biophysical measurements can be combined with classical analysis approaches of tumor biology. The insights into physical interactions between cancer cells, the endothelium and the microenvironment may help to answer some "old," but still important questions in cancer disease progression.

Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

NASA Astrophysics Data System (ADS)

Mierke, Claudia T.

2015-10-01

There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present current cancer research in a different light from a physical point of view with respect to cancer cell mechanics and the special and unique role of the endothelium on cancer cell invasion. The physical view on cancer disease may lead to novel insights into cancer disease and will help to overcome the classical views on cancer. In addition, in this review it will be discussed how physics of cancer can help to reveal and propose the functional mechanism which cancer cells use to invade connective tissue and transmigrate through the endothelium to finally metastasize. Finally, in this review it will be demonstrated how biophysical measurements can be combined with classical analysis approaches of tumor biology. The insights into physical interactions between cancer cells, the endothelium and the microenvironment may help to answer some "old," but still important questions in cancer disease progression.

Meaningful crosstalk between biologists and physical scientists is essential for modern biology to progress.

PubMed

Dev, Sukhendu B

2009-01-01

The advances in biological sciences have been phenomenal since the structure of DNA was decoded, especially if one considers the input from physical sciences, not only in terms of analytical tools, but also understanding and solving some of the key problems in biology. In this article, I trace briefly the history of this transition, from physical sciences to biology, and argue that progress in modern biology can be accelerated if there is far more meaningful crosstalk between the biologists and the physical scientists, simply because biology has become far more complex and interdisciplinary, and the need for such crosstalk cannot be overemphasized. Without a concerted effort in this area progress will be hindered, and the two camps will continue to work on their own, using their own specialized language, thus making communication highly ineffective. I support my argument giving a vast array of examples and also quoting leading authorities.

The system spatial-frequency filtering of birefringence images of human blood layers

NASA Astrophysics Data System (ADS)

Ushenko, A. G.; Boychuk, T. M.; Mincer, O. P.; Angelsky, P. O.; Bodnar, N. B.; Oleinichenko, B. P.; Bizer, L. I.

2013-09-01

Among various opticophysical methods [1 - 3] of diagnosing the structure and properties of the optical anisotropic component of various biological objects a specific trend has been singled out - multidimensional laser polarimetry of microscopic images of the biological tissues with the following statistic, correlative and fractal analysis of the coordinate distributions of the azimuths and ellipticity of polarization in approximating of linear birefringence polycrystalline protein networks [4 - 10]. At the same time, in most cases, experimental obtaining of tissue sample is a traumatic biopsy operation. In addition, the mechanisms of transformation of the state of polarization of laser radiation by means of the opticoanisotropic biological structures are more varied (optical dichroism, circular birefringence). Hereat, real polycrystalline networks can be formed by different types, both in size and optical properties of biological crystals. Finally, much more accessible for an experimental investigation are biological fluids such as blood, bile, urine, and others. Thus, further progress of laser polarimetry can be associated with the development of new methods of analysis and processing (selection) of polarization- heterogeneous images of biological tissues and fluids, taking into account a wider set of mechanisms anisotropic mechanisms. Our research is aimed at developing experimental method of the Fourier polarimetry and a spatialfrequency selection for distributions of the azimuth and the ellipticity polarization of blood plasma laser images with a view of diagnosing prostate cancer.

Ubiquitin modifications

PubMed Central

Swatek, Kirby N; Komander, David

2016-01-01

Protein ubiquitination is a dynamic multifaceted post-translational modification involved in nearly all aspects of eukaryotic biology. Once attached to a substrate, the 76-amino acid protein ubiquitin is subjected to further modifications, creating a multitude of distinct signals with distinct cellular outcomes, referred to as the 'ubiquitin code'. Ubiquitin can be ubiquitinated on seven lysine (Lys) residues or on the N-terminus, leading to polyubiquitin chains that can encompass complex topologies. Alternatively or in addition, ubiquitin Lys residues can be modified by ubiquitin-like molecules (such as SUMO or NEDD8). Finally, ubiquitin can also be acetylated on Lys, or phosphorylated on Ser, Thr or Tyr residues, and each modification has the potential to dramatically alter the signaling outcome. While the number of distinctly modified ubiquitin species in cells is mind-boggling, much progress has been made to characterize the roles of distinct ubiquitin modifications, and many enzymes and receptors have been identified that create, recognize or remove these ubiquitin modifications. We here provide an overview of the various ubiquitin modifications present in cells, and highlight recent progress on ubiquitin chain biology. We then discuss the recent findings in the field of ubiquitin acetylation and phosphorylation, with a focus on Ser65-phosphorylation and its role in mitophagy and Parkin activation. PMID:27012465

Olympic Fisher Reintroduction Project: Progress report 2008-2011

USGS Publications Warehouse

Jeffrey C. Lewis,; Patti J. Happe,; Jenkins, Kurt J.; Manson, David J.

2012-01-01

This progress report summarizes the final year of activities of Phase I of the Olympic fisher restoration project. The intent of the Olympic fisher reintroduction project is to reestablish a self-sustaining population of fishers on the Olympic Peninsula. To achieve this goal, the Olympic fisher reintroduction project released 90 fishers within Olympic National Park from 2008 to 2010. The reintroduction of fishers to the Olympic Peninsula was designed as an adaptive management project, including the monitoring of released fishers as a means to (1) evaluate reintroduction success, (2) investigate key biological and ecological traits of fishers, and (3) inform future reintroduction, monitoring, and research efforts. This report summarizes reintroduction activities and preliminary research and monitoring results completed through December 2011. The report is non-interpretational in nature. Although we report the status of movement, survival, and home range components of the research, we have not completed final analyses and interpretation of research results. Much of the data collected during the monitoring and research project will be analyzed and interpreted in the doctoral dissertation being developed by Jeff Lewis; the completion of this dissertation is anticipated prior to April 2013. We anticipate that this work, and analyses of other data collected during the project, will result in several peer-reviewed scientific publications in ecological and conservation journals, which collectively will comprise the final reporting of work summarized here. These publications will include papers addressing post-release movements, survival, resource selection, food habits, and age determination of fishers.

Function and Biosynthesis of Cell Wall α-1,3-Glucan in Fungi

PubMed Central

Yoshimi, Akira; Miyazawa, Ken; Abe, Keietsu

2017-01-01

Although α-1,3-glucan is a major cell wall polysaccharide in filamentous fungi, its biological functions remain unclear, except that it acts as a virulence factor in animal and plant pathogenic fungi: it conceals cell wall β-glucan on the fungal cell surface to circumvent recognition by hosts. However, cell wall α-1,3-glucan is also present in many of non-pathogenic fungi. Recently, the universal function of α-1,3-glucan as an aggregation factor has been demonstrated. Applications of fungi with modified cell wall α-1,3-glucan in the fermentation industry and of in vitro enzymatically-synthesized α-1,3-glucan in bio-plastics have been developed. This review focuses on the recent progress in our understanding of the biological functions and biosynthetic mechanism of cell wall α-1,3-glucan in fungi. We briefly consider the history of studies on α-1,3-glucan, overview its biological functions and biosynthesis, and finally consider the industrial applications of fungi deficient in α-1,3-glucan. PMID:29371579

Machine metaphors and ethics in synthetic biology.

PubMed

Boldt, Joachim

2018-06-04

The extent to which machine metaphors are used in synthetic biology is striking. These metaphors contain a specific perspective on organisms as well as on scientific and technological progress. Expressions such as "genetically engineered machine", "genetic circuit", and "platform organism", taken from the realms of electronic engineering, car manufacturing, and information technology, highlight specific aspects of the functioning of living beings while at the same time hiding others, such as evolutionary change and interdependencies in ecosystems. Since these latter aspects are relevant for, for example, risk evaluation of uncontained uses of synthetic organisms, it is ethically imperative to resist the thrust of machine metaphors in this respect. In addition, from the perspective of the machine metaphor viewing an entity as a moral agent or patient becomes dubious. If one were to regard living beings, including humans, as machines, it becomes difficult to justify ascriptions of moral status. Finally, the machine metaphor reinforces beliefs in the potential of synthetic biology to play a decisive role in solving societal problems, and downplays the role of alternative technological, and social and political measures.

[Sixty years ago, cell cultures finally permitted the poliomyelitis virus to multiply easily].

PubMed

Chastel, Claude

2009-01-01

In 1949, three American virologists, John F. Enders, Thomas H. Weller and Frederick C. Robbins, from the Harvard Medical Scholl and working at the Children's Medical Centre, Boston, Mass., have provoked a true revolution in Virology. Here, they have succeeded in readily multiplying the three poliomyelitis viruses in vitro, in non-nervous cells cultures. A few years afterwards (1954), they were collectively honoured by the Nobel Prize of Physiology and Medicine. This discovery not only has quickly led to the production of efficient poliomyelitis vaccines (J. E. Salk, 1953; A. B. Sabin, 1955) but also has permitted to easily isolate a number of already known viruses (measles, rubella, mumps, herpes simplex and herpes zoster) or until then totally unknown viruses (adenovirus, echovirus, cytomegalovirus). These progresses have significantly contributed to improve diagnosis, sanitary surveillance and vaccinal prophylaxis of human and animal viral diseases. Moreover, the cells cultures techniques have also benefited to other domains of fundamental Biology, such as cellular biology, genetics, cancerology, biology of the reproduction and regenerative medicine as well.

Liposomes as nanomedical devices

PubMed Central

Bozzuto, Giuseppina; Molinari, Agnese

2015-01-01

Since their discovery in the 1960s, liposomes have been studied in depth, and they continue to constitute a field of intense research. Liposomes are valued for their biological and technological advantages, and are considered to be the most successful drug-carrier system known to date. Notable progress has been made, and several biomedical applications of liposomes are either in clinical trials, are about to be put on the market, or have already been approved for public use. In this review, we briefly analyze how the efficacy of liposomes depends on the nature of their components and their size, surface charge, and lipidic organization. Moreover, we discuss the influence of the physicochemical properties of liposomes on their interaction with cells, half-life, ability to enter tissues, and final fate in vivo. Finally, we describe some strategies developed to overcome limitations of the “first-generation” liposomes, and liposome-based drugs on the market and in clinical trials. PMID:25678787

Prebiotic organic matter - Possible pathways for synthesis in a geological context

NASA Technical Reports Server (NTRS)

Chang, S.

1982-01-01

Models for the accretion of the earth, core formation, differentiation of the planet into core, mantle, crust, and atmosphere, and prebiotic synthesis of organic materials are reviewed. The development of the Haldane-Oparin and Urey models is traced, and the effect of accretion time on the outgassing process and the composition of the consequent atmosphere is examined. Model prebiotic atmospheres are calculated, the extent of equilibration of the primitive atmosphere is studied and the evolution of the atmosphere prior to organic chemical evolution is reviewed. Finally, experimental progress in synthesis of biological monomers and polymers under presumed early earth conditions is covered.

TRACING CO-REGULATORY NETWORK DYNAMICS IN NOISY, SINGLE-CELL TRANSCRIPTOME TRAJECTORIES.

PubMed

Cordero, Pablo; Stuart, Joshua M

2017-01-01

The availability of gene expression data at the single cell level makes it possible to probe the molecular underpinnings of complex biological processes such as differentiation and oncogenesis. Promising new methods have emerged for reconstructing a progression 'trajectory' from static single-cell transcriptome measurements. However, it remains unclear how to adequately model the appreciable level of noise in these data to elucidate gene regulatory network rewiring. Here, we present a framework called Single Cell Inference of MorphIng Trajectories and their Associated Regulation (SCIMITAR) that infers progressions from static single-cell transcriptomes by employing a continuous parametrization of Gaussian mixtures in high-dimensional curves. SCIMITAR yields rich models from the data that highlight genes with expression and co-expression patterns that are associated with the inferred progression. Further, SCIMITAR extracts regulatory states from the implicated trajectory-evolvingco-expression networks. We benchmark the method on simulated data to show that it yields accurate cell ordering and gene network inferences. Applied to the interpretation of a single-cell human fetal neuron dataset, SCIMITAR finds progression-associated genes in cornerstone neural differentiation pathways missed by standard differential expression tests. Finally, by leveraging the rewiring of gene-gene co-expression relations across the progression, the method reveals the rise and fall of co-regulatory states and trajectory-dependent gene modules. These analyses implicate new transcription factors in neural differentiation including putative co-factors for the multi-functional NFAT pathway.

CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett's Esophagus Malignant Progression.

PubMed

Cardoso, Joana; Mesquita, Marta; Dias Pereira, António; Bettencourt-Dias, Mónica; Chaves, Paula; Pereira-Leal, José B

2016-01-01

Barrett's esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett's malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett's progression, CYR61 and TAZ. Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that CYR61 and TAZ have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett's samples associated with high-grade dysplasia/adenocarcinoma. In our cohort CYR61 and TAZ up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett's esophagus index samples. Finally, we found that CYR61 and TAZ over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both CYR61 and TAZ genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett's esophagus neoplastic progression.

FERN - a Java framework for stochastic simulation and evaluation of reaction networks.

PubMed

Erhard, Florian; Friedel, Caroline C; Zimmer, Ralf

2008-08-29

Stochastic simulation can be used to illustrate the development of biological systems over time and the stochastic nature of these processes. Currently available programs for stochastic simulation, however, are limited in that they either a) do not provide the most efficient simulation algorithms and are difficult to extend, b) cannot be easily integrated into other applications or c) do not allow to monitor and intervene during the simulation process in an easy and intuitive way. Thus, in order to use stochastic simulation in innovative high-level modeling and analysis approaches more flexible tools are necessary. In this article, we present FERN (Framework for Evaluation of Reaction Networks), a Java framework for the efficient simulation of chemical reaction networks. FERN is subdivided into three layers for network representation, simulation and visualization of the simulation results each of which can be easily extended. It provides efficient and accurate state-of-the-art stochastic simulation algorithms for well-mixed chemical systems and a powerful observer system, which makes it possible to track and control the simulation progress on every level. To illustrate how FERN can be easily integrated into other systems biology applications, plugins to Cytoscape and CellDesigner are included. These plugins make it possible to run simulations and to observe the simulation progress in a reaction network in real-time from within the Cytoscape or CellDesigner environment. FERN addresses shortcomings of currently available stochastic simulation programs in several ways. First, it provides a broad range of efficient and accurate algorithms both for exact and approximate stochastic simulation and a simple interface for extending to new algorithms. FERN's implementations are considerably faster than the C implementations of gillespie2 or the Java implementations of ISBJava. Second, it can be used in a straightforward way both as a stand-alone program and within new systems biology applications. Finally, complex scenarios requiring intervention during the simulation progress can be modelled easily with FERN.

White Adipose Tissue Cells Are Recruited by Experimental Tumors and Promote Cancer Progression in Mouse Models

PubMed Central

Zhang, Yan; Daquinag, Alexes; Traktuev, Dmitry O.; Amaya-Manzanares, Felipe; Simmons, Paul J.; March, Keith L.; Pasqualini, Renata; Arap, Wadih; Kolonin, Mikhail G.

2010-01-01

The connection between obesity and accelerated cancer progression has been established, but the mediating mechanisms are not well understood. We have shown that stromal cells from white adipose tissue (WAT) cooperate with the endothelium to promote blood vessel formation through the secretion of soluble trophic factors. Here, we hypothesize that WAT directly mediates cancer progression by serving as a source of cells that migrate to tumors and promote neovascularization. To test this hypothesis, we have evaluated the recruitment of WAT-derived cells by tumors and the effect of their engraftment on tumor growth by integrating a transgenic mouse strain engineered for expansion of traceable cells with established allograft and xenograft cancer models. Our studies show that entry of adipose stromal and endothelial cells into systemic circulation leads to their homing to and engraftment into tumor stroma and vasculature, respectively. We show that recruitment of adipose stromal cells by tumors is sufficient to promote tumor growth. Finally, we show that migration of stromal and vascular progenitor cells from WAT grafts to tumors is also associated with acceleration of cancer progression. These results provide a biological insight for the clinical association between obesity and cancer, thus outlining potential avenues for preventive and therapeutic strategies. PMID:19491274

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer.

PubMed

Carducci, Michael A; Saad, Fred; Abrahamsson, Per-Anders; Dearnaley, David P; Schulman, Claude C; North, Scott A; Sleep, Darryl J; Isaacson, Jeffrey D; Nelson, Joel B

2007-11-01

The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone-refractory prostate cancer (HRPC). This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P = .136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P < .05 for each). The median time to BAP progression (>/=50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P < .01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden.

Thermal modeling for pulsed radiofrequency ablation: analytical study based on hyperbolic heat conduction.

PubMed

López Molina, Juan A; Rivera, María J; Trujillo, Macarena; Berjano, Enrique J

2009-04-01

The objectives of this study were to model the temperature progress of a pulsed radiofrequency (RF) power during RF heating of biological tissue, and to employ the hyperbolic heat transfer equation (HHTE), which takes the thermal wave behavior into account, and compare the results to those obtained using the heat transfer equation based on Fourier theory (FHTE). A theoretical model was built based on an active spherical electrode completely embedded in the biological tissue, after which HHTE and FHTE were analytically solved. We found three typical waveforms for the temperature progress depending on the relations between the dimensionless duration of the RF pulse delta(a) and the expression square root of lambda(rho-1), with lambda as the dimensionless thermal relaxation time of the tissue and rho as the dimensionless position. In the case of a unique RF pulse, the temperature at any location was the result of the overlapping of two different heat sources delayed for a duration delta(a) (each heat source being produced by a RF pulse of limitless duration). The most remarkable feature in the HHTE analytical solution was the presence of temperature peaks traveling through the medium at a finite speed. These peaks not only occurred during the RF power switch-on period but also during switch off. Finally, a physical explanation for these temperature peaks is proposed based on the interaction of forward and reverse thermal waves. All-purpose analytical solutions for FHTE and HHTE were obtained during pulsed RF heating of biological tissues, which could be used for any value of pulsing frequency and duty cycle.

Advances on plant-pathogen interactions from molecular toward systems biology perspectives.

PubMed

Peyraud, Rémi; Dubiella, Ullrich; Barbacci, Adelin; Genin, Stéphane; Raffaele, Sylvain; Roby, Dominique

2017-05-01

In the past 2 decades, progress in molecular analyses of the plant immune system has revealed key elements of a complex response network. Current paradigms depict the interaction of pathogen-secreted molecules with host target molecules leading to the activation of multiple plant response pathways. Further research will be required to fully understand how these responses are integrated in space and time, and exploit this knowledge in agriculture. In this review, we highlight systems biology as a promising approach to reveal properties of molecular plant-pathogen interactions and predict the outcome of such interactions. We first illustrate a few key concepts in plant immunity with a network and systems biology perspective. Next, we present some basic principles of systems biology and show how they allow integrating multiomics data and predict cell phenotypes. We identify challenges for systems biology of plant-pathogen interactions, including the reconstruction of multiscale mechanistic models and the connection of host and pathogen models. Finally, we outline studies on resistance durability through the robustness of immune system networks, the identification of trade-offs between immunity and growth and in silico plant-pathogen co-evolution as exciting perspectives in the field. We conclude that the development of sophisticated models of plant diseases incorporating plant, pathogen and climate properties represent a major challenge for agriculture in the future. © 2016 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

[Management of congenital cardiopathies: state of the art].

PubMed

Buendía Hernández, Alfonso; Gloss, Guillermo

2003-01-01

Pediatric cardiology has shown an important development in the last 50 years, the first era was the knowledge of the anatomy of congenital heart defects, then it came the understanding of pathophysiology, the third era is therapeutic and is surgical, the first years with high mortality, but after successful cardiac management in infancy it is less than 10% in complex cardiac defects. Catheterization was useful as a diagnostic tool, nowadays it's used therapeutically, and with good results and in some cases surgery and interventional catheterization are used together in the benefit of patients. All the advances in this field resulted form multidisciplinary progresses, among which one may distinguish the better knowledge of pathology, improvement in pre, trans and post operative assessment and management and progress in operative management. Finally, the understanding of the heart of a child, based in a number of investigative methods to clarify cardiac development, and the molecular biology that will help us to understand the syndromatic associations.

The future of computing--new architectures and new technologies.

PubMed

Warren, P

2004-02-01

All modern computers are designed using the 'von Neumann' architecture and built using silicon transistor technology. Both architecture and technology have been remarkably successful. Yet there are a range of problems for which this conventional architecture is not particularly well adapted, and new architectures are being proposed to solve these problems, in particular based on insight from nature. Transistor technology has enjoyed 50 years of continuing progress. However, the laws of physics dictate that within a relatively short time period this progress will come to an end. New technologies, based on molecular and biological sciences as well as quantum physics, are vying to replace silicon, or at least coexist with it and extend its capability. The paper describes these novel architectures and technologies, places them in the context of the kinds of problems they might help to solve, and predicts their possible manner and time of adoption. Finally it describes some key questions and research problems associated with their use.

Recent Progress of Self-Powered Sensing Systems for Wearable Electronics.

PubMed

Lou, Zheng; Li, La; Wang, Lili; Shen, Guozhen

2017-12-01

Wearable/flexible electronic sensing systems are considered to be one of the key technologies in the next generation of smart personal electronics. To realize personal portable devices with mobile electronics application, i.e., wearable electronic sensors that can work sustainably and continuously without an external power supply are highly desired. The recent progress and advantages of wearable self-powered electronic sensing systems for mobile or personal attachable health monitoring applications are presented. An overview of various types of wearable electronic sensors, including flexible tactile sensors, wearable image sensor array, biological and chemical sensor, temperature sensors, and multifunctional integrated sensing systems is provided. Self-powered sensing systems with integrated energy units are then discussed, separated as energy harvesting self-powered sensing systems, energy storage integrated sensing systems, and all-in-on integrated sensing systems. Finally, the future perspectives of self-powered sensing systems for wearable electronics are discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Progress in the study on mammalian diacylgycerol acyltransgerase (DGAT) gene and its biological function].

PubMed

Wang, Yan; Xu, Heng-Yong; Zhu, Qing

2007-10-01

Diacylglycerol acyltransferase (DGAT; EC 2.3.1.20) is a microsomal enzyme that plays a central role in the metabolism of cellular glycerolipids. DGAT catalyzes the final step in triacylglycerol (TAG) biosynthesis by converting diacylgycerol (DAG) and fatty acyl-coenzyme A (CoA) into triacylglycero1. DGAT plays a fundamental role in the metabolism of cellular diacylglycerol and is important in higher eukaryotes for physiologic processes involving triacylglycerol metabolism such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation. Therefore, DGAT is not only an key factor for control triglycerides and fatty acids, but also may play a key modulatory role in animal fat deposition.

NASA technology utilization applications. [transfer of medical sciences

NASA Technical Reports Server (NTRS)

1973-01-01

The work is reported from September 1972 through August 1973 by the Technology Applications Group of the Science Communication Division (SCD), formerly the Biological Sciences Communication Project (BSCP) in the Department of Medical and Public Affairs of the George Washington University. The work was supportive of many aspects of the NASA Technology Utilization program but in particular those dealing with Biomedical and Technology Application Teams, Applications Engineering projects, new technology reporting and documentation and transfer activities. Of particular interest are detailed reports on the progress of various hardware projects, and suggestions and criteria for the evaluation of candidate hardware projects. Finally some observations about the future expansion of the TU program are offered.

Progress in understanding and overcoming biomass recalcitrance: a BioEnergy Science Center (BESC) perspective

DOE PAGES

Gilna, Paul; Lynd, Lee R.; Mohnen, Debra; ...

2017-11-30

The DOE BioEnergy Science Center has operated as a virtual center with multiple partners for a decade targeting overcoming biomass recalcitrance. BESC has redefined biomass recalcitrance from an observable phenotype to a better understood and manipulatable fundamental and operational property. These manipulations are then the result of deeper biological understanding and can be combined with other advanced biotechnology improvements in biomass conversion to improve bioenergy processes and markets. This article provides an overview of key accomplishments in overcoming recalcitrance via better plants, better microbes, and better tools and combinations. Finally, we present a perspective on the aspects of successful centermore » operation.« less

Progress in understanding and overcoming biomass recalcitrance: a BioEnergy Science Center (BESC) perspective

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

Gilna, Paul; Lynd, Lee R.; Mohnen, Debra

The DOE BioEnergy Science Center has operated as a virtual center with multiple partners for a decade targeting overcoming biomass recalcitrance. BESC has redefined biomass recalcitrance from an observable phenotype to a better understood and manipulatable fundamental and operational property. These manipulations are then the result of deeper biological understanding and can be combined with other advanced biotechnology improvements in biomass conversion to improve bioenergy processes and markets. This article provides an overview of key accomplishments in overcoming recalcitrance via better plants, better microbes, and better tools and combinations. Finally, we present a perspective on the aspects of successful centermore » operation.« less

Fiber Optic Surface Plasmon Resonance-Based Biosensor Technique: Fabrication, Advancement, and Application.

PubMed

Liang, Gaoling; Luo, Zewei; Liu, Kunping; Wang, Yimin; Dai, Jianxiong; Duan, Yixiang

2016-05-03

Fiber optic-based biosensors with surface plasmon resonance (SPR) technology are advanced label-free optical biosensing methods. They have brought tremendous progress in the sensing of various chemical and biological species. This review summarizes four sensing configurations (prism, grating, waveguide, and fiber optic) with two ways, attenuated total reflection (ATR) and diffraction, to excite the surface plasmons. Meanwhile, the designs of different probes (U-bent, tapered, and other probes) are also described. Finally, four major types of biosensors, immunosensor, DNA biosensor, enzyme biosensor, and living cell biosensor, are discussed in detail for their sensing principles and applications. Future prospects of fiber optic-based SPR sensor technology are discussed.

CYR61 and TAZ Upregulation and Focal Epithelial to Mesenchymal Transition May Be Early Predictors of Barrett’s Esophagus Malignant Progression

PubMed Central

Mesquita, Marta; Dias Pereira, António; Bettencourt-Dias, Mónica; Chaves, Paula; Pereira-Leal, José B.

2016-01-01

Barrett’s esophagus is the major risk factor for esophageal adenocarcinoma. It has a low but non-neglectable risk, high surveillance costs and no reliable risk stratification markers. We sought to identify early biomarkers, predictive of Barrett’s malignant progression, using a meta-analysis approach on gene expression data. This in silico strategy was followed by experimental validation in a cohort of patients with extended follow up from the Instituto Português de Oncologia de Lisboa de Francisco Gentil EPE (Portugal). Bioinformatics and systems biology approaches singled out two candidate predictive markers for Barrett’s progression, CYR61 and TAZ. Although previously implicated in other malignancies and in epithelial-to-mesenchymal transition phenotypes, our experimental validation shows for the first time that CYR61 and TAZ have the potential to be predictive biomarkers for cancer progression. Experimental validation by reverse transcriptase quantitative PCR and immunohistochemistry confirmed the up-regulation of both genes in Barrett’s samples associated with high-grade dysplasia/adenocarcinoma. In our cohort CYR61 and TAZ up-regulation ranged from one to ten years prior to progression to adenocarcinoma in Barrett’s esophagus index samples. Finally, we found that CYR61 and TAZ over-expression is correlated with early focal signs of epithelial to mesenchymal transition. Our results highlight both CYR61 and TAZ genes as potential predictive biomarkers for stratification of the risk for development of adenocarcinoma and suggest a potential mechanistic route for Barrett’s esophagus neoplastic progression. PMID:27583562

The biology and therapeutic management of melanoma brain metastases.

PubMed

Abate-Daga, Daniel; Ramello, Maria C; Smalley, Inna; Forsyth, Peter A; Smalley, Keiran S M

2018-07-01

The recent years have seen significant progress in the development of systemic therapies to treat patients with advanced melanoma. Use of these new treatment modalities, which include immune checkpoint inhibitors and small molecule BRAF inhibitors, lead to increased overall survival and better outcomes. Although revolutionary, these therapies are often less effective against melanoma brain metastases, and frequently the CNS is the major site of treatment failure. The development of brain metastases remains a serious complication of advanced melanoma that is associated with significant morbidity and mortality. New approaches to both prevent the development of brain metastases and treat established disease are urgently needed. In this review we will outline the mechanisms underlying the development of melanoma brain metastases and will discuss how new insights into metastasis biology are driving the development of new therapeutic strategies. Finally, we will describe the latest data from the ongoing clinical trials for patients with melanoma brain metastases. Copyright © 2018 Elsevier Inc. All rights reserved.

Three-dimensional nano-biointerface as a new platform for guiding cell fate.

PubMed

Liu, Xueli; Wang, Shutao

2014-04-21

Three-dimensional nano-biointerface has been emerging as an important topic for chemistry, nanotechnology, and life sciences in recent years. Understanding the exchanges of materials, signals, and energy at biological interfaces has inspired and helped the serial design of three-dimensional nano-biointerfaces. The intimate interactions between cells and nanostructures bring many novel properties, making three-dimensional nano-biointerfaces a powerful platform to guide cell fate in a controllable and accurate way. These advantages and capabilities endow three-dimensional nano-biointerfaces with an indispensable role in developing advanced biological science and technology. This tutorial review is mainly focused on the recent progress of three-dimensional nano-biointerfaces and highlights the new explorations and unique phenomena of three-dimensional nano-biointerfaces for cell-related fundamental studies and biomedical applications. Some basic bio-inspired principles for the design and creation of three-dimensional nano-biointerfaces are also delivered in this review. Current and further challenges of three-dimensional nano-biointerfaces are finally addressed and proposed.

Advances in Translational Research in Neuro-oncology

PubMed Central

Fueyo, Juan; Gomez-Manzano, Candelaria; Yung, W. K. Alfred

2011-01-01

During the last decade, we have witnessed several key advances in the field of neurooncology. First, there were conceptual advances in the molecular and cell biology of malignant gliomas including the discovery in 2004 of brain tumor stem cells. Second, the Cancer Genome Atlas project has been extremely useful in the discovery of new molecular markers, including mutations in the IDH1 gene, and has led to a new classification of gliomas based on the differentiation status and mesenchymal transformation. In addition, use of the 1p/19q marker and O6-methylguanine-DNA methyltransferase methylation status have been identified as guides for patient selection for therapies and represent the first steps toward personalized medicine for treating gliomas. Finally, progress has been made in treatment strategies including the establishment of temozolomide as the criterion standard for treating gliomas, the adoption of bevacizumab in the clinical setting, and developments in experimental biological therapies including cancer vaccines and oncolytic adenoviruses. PMID:21059986

Why sleep is important for health: a psychoneuroimmunology perspective.

PubMed

Irwin, Michael R

2015-01-03

Sleep has a critical role in promoting health. Research over the past decade has documented that sleep disturbance has a powerful influence on the risk of infectious disease, the occurrence and progression of several major medical illnesses including cardiovascular disease and cancer, and the incidence of depression. Increasingly, the field has focused on identifying the biological mechanisms underlying these effects. This review highlights the impact of sleep on adaptive and innate immunity, with consideration of the dynamics of sleep disturbance, sleep restriction, and insomnia on (a) antiviral immune responses with consequences for vaccine responses and infectious disease risk and (b) proinflammatory immune responses with implications for cardiovascular disease, cancer, and depression. This review also discusses the neuroendocrine and autonomic neural underpinnings linking sleep disturbance and immunity and the reciprocal links between sleep and inflammatory biology. Finally, interventions are discussed as effective strategies to improve sleep, and potential opportunities are identified to promote sleep health for therapeutic control of chronic infectious, inflammatory, and neuropsychiatric diseases.

Biomechanical forces in the skeleton and their relevance to bone metastasis: biology and engineering considerations.

PubMed

Lynch, Maureen E; Fischbach, Claudia

2014-12-15

Bone metastasis represents the leading cause of breast cancer related-deaths. However, the effect of skeleton-associated biomechanical signals on the initiation, progression, and therapy response of breast cancer bone metastasis is largely unknown. This review seeks to highlight possible functional connections between skeletal mechanical signals and breast cancer bone metastasis and their contribution to clinical outcome. It provides an introduction to the physical and biological signals underlying bone functional adaptation and discusses the modulatory roles of mechanical loading and breast cancer metastasis in this process. Following a definition of biophysical design criteria, in vitro and in vivo approaches from the fields of bone biomechanics and tissue engineering that may be suitable to investigate breast cancer bone metastasis as a function of varied mechano-signaling will be reviewed. Finally, an outlook of future opportunities and challenges associated with this newly emerging field will be provided. Copyright © 2014 Elsevier B.V. All rights reserved.

WKB theory of large deviations in stochastic populations

NASA Astrophysics Data System (ADS)

Assaf, Michael; Meerson, Baruch

2017-06-01

Stochasticity can play an important role in the dynamics of biologically relevant populations. These span a broad range of scales: from intra-cellular populations of molecules to population of cells and then to groups of plants, animals and people. Large deviations in stochastic population dynamics—such as those determining population extinction, fixation or switching between different states—are presently in a focus of attention of statistical physicists. We review recent progress in applying different variants of dissipative WKB approximation (after Wentzel, Kramers and Brillouin) to this class of problems. The WKB approximation allows one to evaluate the mean time and/or probability of population extinction, fixation and switches resulting from either intrinsic (demographic) noise, or a combination of the demographic noise and environmental variations, deterministic or random. We mostly cover well-mixed populations, single and multiple, but also briefly consider populations on heterogeneous networks and spatial populations. The spatial setting also allows one to study large fluctuations of the speed of biological invasions. Finally, we briefly discuss possible directions of future work.

USHERING IN THE STUDY AND TREATMENT OF PRECLINICAL ALZHEIMER DISEASE

PubMed Central

Langbaum, Jessica B.S.; Fleisher, Adam S.; Chen, Kewei; Ayutyanont, Napatkamon; Lopera, Francisco; Quiroz, Yakeel T.; Caselli, Richard J.; Tariot, Pierre N.; Reiman, Eric M.

2014-01-01

Researchers have begun to characterize the subtle biological and cognitive processes that precede the clinical onset of Alzheimer disease (AD), and to set the stage for accelerated evaluation of experimental treatments to delay the onset, reduce the risk of or completely prevent clinical decline. Here, we provide an overview of the experimental strategies, and brain imaging and cerebrospinal fluid biomarker measures that are used in early detection and tracking of AD, highlighting at-risk individuals who could be suitable for preclinical monitoring. We discuss how these advances have contributed to reconceptualization of AD as a sequence of biological changes that occur during progression from preclinical AD, to mild cognitive impairment and finally dementia, and we review recently proposed research criteria for preclinical AD. Advances in the study of preclinical AD have driven the recognition that efficacy of at least some AD therapies may depend on initiation of treatment before clinical manifestation of disease, leading to a new era of AD prevention research. PMID:23752908

Actualities and Perspectives in Neurosurgery

PubMed Central

Iencean, SM; Brehar, FM

2008-01-01

In the field of neurosurgery, like in other surgical specialties, the last decades have brought major achievements. The series of revolutionary discoveries has started during the last century in the fifties, with stereotactic radiosurgery, then continued with the implementation of operative microscope (during the seventies), the endovascular embolisation in the nineties and finally with the major improvement in robotic neurosurgery and molecular neurosurgery at the beginning of this century. The major innovation has been brought not only in the field of therapeutical measures but also in the field of neuro– imaging. Thus, the modern MRI with more than 3 Tesla, can reveal to the neurosurgeon the most intimate structures of the nervous system. Several important areas in neurosurgery like: vascular neurosurgery, functional neurosurgery and brain tumors pathology, benefit from the modern technology and from the latest discoveries from genetic and molecular biology. In conclusion, summarizing the discoveries of the last decade, we emphasize that the related areas like genetics, molecular biology, computer technology become more and more important in the future progress of the neurosurgery. PMID:20108475

Ushering in the study and treatment of preclinical Alzheimer disease.

PubMed

Langbaum, Jessica B; Fleisher, Adam S; Chen, Kewei; Ayutyanont, Napatkamon; Lopera, Francisco; Quiroz, Yakeel T; Caselli, Richard J; Tariot, Pierre N; Reiman, Eric M

2013-07-01

Researchers have begun to characterize the subtle biological and cognitive processes that precede the clinical onset of Alzheimer disease (AD), and to set the stage for accelerated evaluation of experimental treatments to delay the onset, reduce the risk of, or completely prevent clinical decline. In this Review, we provide an overview of the experimental strategies, and brain imaging and cerebrospinal fluid biomarker measures that are used in early detection and tracking of AD, highlighting at-risk individuals who could be suitable for preclinical monitoring. We discuss how advances in the field have contributed to reconceptualization of AD as a sequence of biological changes that occur during progression from preclinical AD, to mild cognitive impairment and finally dementia, and we review recently proposed research criteria for preclinical AD. Advances in the study of preclinical AD have driven the recognition that efficacy of at least some AD therapies may depend on initiation of treatment before clinical manifestation of disease, leading to a new era of AD prevention research.

malERA: An updated research agenda for characterising the reservoir and measuring transmission in malaria elimination and eradication

PubMed Central

2017-01-01

This paper summarises key advances in defining the infectious reservoir for malaria and the measurement of transmission for research and programmatic use since the Malaria Eradication Research Agenda (malERA) publication in 2011. Rapid and effective progress towards elimination requires an improved understanding of the sources of transmission as well as those at risk of infection. Characterising the transmission reservoir in different settings will enable the most appropriate choice, delivery, and evaluation of interventions. Since 2011, progress has been made in a number of areas. The extent of submicroscopic and asymptomatic infections is better understood, as are the biological parameters governing transmission of sexual stage parasites. Limitations of existing transmission measures have been documented, and proof-of-concept has been established for new innovative serological and molecular methods to better characterise transmission. Finally, there now exists a concerted effort towards the use of ensemble datasets across the spectrum of metrics, from passive and active sources, to develop more accurate risk maps of transmission. These can be used to better target interventions and effectively monitor progress toward elimination. The success of interventions depends not only on the level of endemicity but also on how rapidly or recently an area has undergone changes in transmission. Improved understanding of the biology of mosquito–human and human–mosquito transmission is needed particularly in low-endemic settings, where heterogeneity of infection is pronounced and local vector ecology is variable. New and improved measures of transmission need to be operationally feasible for the malaria programmes. Outputs from these research priorities should allow the development of a set of approaches (applicable to both research and control programmes) that address the unique challenges of measuring and monitoring transmission in near-elimination settings and defining the absence of transmission. PMID:29190279

Advances of Molecular Imaging for Monitoring the Anatomical and Functional Architecture of the Olfactory System.

PubMed

Zhang, Xintong; Bi, Anyao; Gao, Quansheng; Zhang, Shuai; Huang, Kunzhu; Liu, Zhiguo; Gao, Tang; Zeng, Wenbin

2016-01-20

The olfactory system of organisms serves as a genetically and anatomically model for studying how sensory input can be translated into behavior output. Some neurologic diseases are considered to be related to olfactory disturbance, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis, and so forth. However, it is still unclear how the olfactory system affects disease generation processes and olfaction delivery processes. Molecular imaging, a modern multidisciplinary technology, can provide valid tools for the early detection and characterization of diseases, evaluation of treatment, and study of biological processes in living subjects, since molecular imaging applies specific molecular probes as a novel approach to produce special data to study biological processes in cellular and subcellular levels. Recently, molecular imaging plays a key role in studying the activation of olfactory system, thus it could help to prevent or delay some diseases. Herein, we present a comprehensive review on the research progress of the imaging probes for visualizing olfactory system, which is classified on different imaging modalities, including PET, MRI, and optical imaging. Additionally, the probes' design, sensing mechanism, and biological application are discussed. Finally, we provide an outlook for future studies in this field.

Disrupted Signaling through the Fanconi Anemia Pathway Leads to Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

PubMed Central

Geiselhart, Anja; Lier, Amelie; Walter, Dagmar; Milsom, Michael D.

2012-01-01

Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC). This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients. PMID:22675615

The effects of dynamic loading on the intervertebral disc.

PubMed

Chan, Samantha C W; Ferguson, Stephen J; Gantenbein-Ritter, Benjamin

2011-11-01

Loading is important to maintain the balance of matrix turnover in the intervertebral disc (IVD). Daily cyclic diurnal assists in the transport of large soluble factors across the IVD and its surrounding circulation and applies direct and indirect stimulus to disc cells. Acute mechanical injury and accumulated overloading, however, could induce disc degeneration. Recently, there is more information available on how cyclic loading, especially axial compression and hydrostatic pressure, affects IVD cell biology. This review summarises recent studies on the response of the IVD and stem cells to applied cyclic compression and hydrostatic pressure. These studies investigate the possible role of loading in the initiation and progression of disc degeneration as well as quantifying a physiological loading condition for the study of disc degeneration biological therapy. Subsequently, a possible physiological/beneficial loading range is proposed. This physiological/beneficial loading could provide insight into how to design loading regimes in specific system for the testing of various biological therapies such as cell therapy, chemical therapy or tissue engineering constructs to achieve a better final outcome. In addition, the parameter space of 'physiological' loading may also be an important factor for the differentiation of stem cells towards most ideally 'discogenic' cells for tissue engineering purpose.

78 FR 38028 - Duke Energy Progress, Inc.; Notice of Video Conference To Discuss Yadkin-Pee Dee Hydroelectric...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-25

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 2206-030] Duke Energy Progress, Inc.; Notice of Video Conference To Discuss Yadkin-Pee Dee Hydroelectric Project Biological...), NMFS will host a video conference to describe and discuss the terms and conditions in the Biological...

Freshwater Biological Traits Database (Final Report)

EPA Science Inventory

EPA announced the release of the final report, Freshwater Biological Traits Database. This report discusses the development of a database of freshwater biological traits. The database combines several existing traits databases into an online format. The database is also...

Enhancement of COPD biological networks using a web-based collaboration interface

PubMed Central

Boue, Stephanie; Fields, Brett; Hoeng, Julia; Park, Jennifer; Peitsch, Manuel C.; Schlage, Walter K.; Talikka, Marja; Binenbaum, Ilona; Bondarenko, Vladimir; Bulgakov, Oleg V.; Cherkasova, Vera; Diaz-Diaz, Norberto; Fedorova, Larisa; Guryanova, Svetlana; Guzova, Julia; Igorevna Koroleva, Galina; Kozhemyakina, Elena; Kumar, Rahul; Lavid, Noa; Lu, Qingxian; Menon, Swapna; Ouliel, Yael; Peterson, Samantha C.; Prokhorov, Alexander; Sanders, Edward; Schrier, Sarah; Schwaitzer Neta, Golan; Shvydchenko, Irina; Tallam, Aravind; Villa-Fombuena, Gema; Wu, John; Yudkevich, Ilya; Zelikman, Mariya

2015-01-01

The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website ( https://bionet.sbvimprover.com/) and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD-relevant models that can be used to help understand the mechanisms related to lung pathobiology. Registered users of the website can freely browse and download the networks. PMID:25767696

Enhancement of COPD biological networks using a web-based collaboration interface.

PubMed

Boue, Stephanie; Fields, Brett; Hoeng, Julia; Park, Jennifer; Peitsch, Manuel C; Schlage, Walter K; Talikka, Marja; Binenbaum, Ilona; Bondarenko, Vladimir; Bulgakov, Oleg V; Cherkasova, Vera; Diaz-Diaz, Norberto; Fedorova, Larisa; Guryanova, Svetlana; Guzova, Julia; Igorevna Koroleva, Galina; Kozhemyakina, Elena; Kumar, Rahul; Lavid, Noa; Lu, Qingxian; Menon, Swapna; Ouliel, Yael; Peterson, Samantha C; Prokhorov, Alexander; Sanders, Edward; Schrier, Sarah; Schwaitzer Neta, Golan; Shvydchenko, Irina; Tallam, Aravind; Villa-Fombuena, Gema; Wu, John; Yudkevich, Ilya; Zelikman, Mariya

2015-01-01

The construction and application of biological network models is an approach that offers a holistic way to understand biological processes involved in disease. Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disease of the airways for which therapeutic options currently are limited after diagnosis, even in its earliest stage. COPD network models are important tools to better understand the biological components and processes underlying initial disease development. With the increasing amounts of literature that are now available, crowdsourcing approaches offer new forms of collaboration for researchers to review biological findings, which can be applied to the construction and verification of complex biological networks. We report the construction of 50 biological network models relevant to lung biology and early COPD using an integrative systems biology and collaborative crowd-verification approach. By combining traditional literature curation with a data-driven approach that predicts molecular activities from transcriptomics data, we constructed an initial COPD network model set based on a previously published non-diseased lung-relevant model set. The crowd was given the opportunity to enhance and refine the networks on a website ( https://bionet.sbvimprover.com/) and to add mechanistic detail, as well as critically review existing evidence and evidence added by other users, so as to enhance the accuracy of the biological representation of the processes captured in the networks. Finally, scientists and experts in the field discussed and refined the networks during an in-person jamboree meeting. Here, we describe examples of the changes made to three of these networks: Neutrophil Signaling, Macrophage Signaling, and Th1-Th2 Signaling. We describe an innovative approach to biological network construction that combines literature and data mining and a crowdsourcing approach to generate a comprehensive set of COPD-relevant models that can be used to help understand the mechanisms related to lung pathobiology. Registered users of the website can freely browse and download the networks.

[Fundamental aspects of extreme aging].

PubMed

Tréton, J

2002-07-01

Major developments in molecular biology in invertebrates have recently shown the determining effect of genetics on aging. The first finding was that artificial selection can highlight the genetic aspect of the aging process, demonstrating the polygenetic property of longevity. Another finding showed that certain gene transfers can modulate the lifespan of an organism. Recent progress has been made in three fields: genetic markers of aging, biological basis of cell maintenance, and hereditary factors contributing to late onset genetic disease. These new developments open new avenues of research in clinical biology. In regard to genetic markers of aging, it has been demonstrated that the ends of the chromosomes, telomeres, play a role in cell senescence. Telomeres can be viewed as markers of aging. Shortened telomeres are associated with replicative senescence and antitumor action. DNA anomalies are also more frequent: simple or double breaks, additions and base substitutions. Data on the biological basis of cell maintenance obtained in invertebrates show the polygenetic property of aging involving four significant mechanisms, control of metabolism, resistance to stress, chromatin-dependent gene regulation of genetic homeostasis. Finally, recent studies have shown that late onset hereditary diseases would be linked with particular genes, some of which have been identified. Two non-exclusive mechanisms could be involved: an adaptive mechanism involving gene selection during the evolutionary process, for example in obesity; and non-adaptive accumulation of gene expression during the post-reproductive phase, for example in Alzheimer's disease. These findings open a new era for the biology of aging.

The molecular biology of WHO grade I astrocytomas.

PubMed

Marko, Nicholas F; Weil, Robert J

2012-12-01

World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.

Space Biology in the 21st century

NASA Technical Reports Server (NTRS)

Halstead, Thora W.; Krauss, Robert W.

1990-01-01

Space Biology is poised to make significant contributions to science in the next century. A carefully crafted, but largely ground-based, program in the United States has evolved major questions that require answers through experiments in space. Science, scientists, and the new long-term spacecrafts designed by NASA will be available for the first time to mount a serious Space Biology effort. The scientific challenge is of such importance that success will provide countless benefits to biologically dependent areas such as medicine, food, and commerce in the decades ahead. The international community is rapidly expanding its role in this field. The United States should generate the resources that will allow progress in Space Biology to match the recognized progress made in aeronautics and the other space sciences.

How to integrate biological research into society and exclude errors in biomedical publications? Progress in theoretical and systems biology releases pressure on experimental research.

PubMed

Volkov, Vadim

2014-01-01

This brief opinion proposes measures to increase efficiency and exclude errors in biomedical research under the existing dynamic situation. Rapid changes in biology began with the description of the three dimensional structure of DNA 60 years ago; today biology has progressed by interacting with computer science and nanoscience together with the introduction of robotic stations for the acquisition of large-scale arrays of data. These changes have had an increasing influence on the entire research and scientific community. Future advance demands short-term measures to ensure error-proof and efficient development. They can include the fast publishing of negative results, publishing detailed methodical papers and excluding a strict connection between career progression and publication activity, especially for younger researchers. Further development of theoretical and systems biology together with the use of multiple experimental methods for biological experiments could also be helpful in the context of years and decades. With regards to the links between science and society, it is reasonable to compare both these systems, to find and describe specific features for biology and to integrate it into the existing stream of social life and financial fluxes. It will increase the level of scientific research and have mutual positive effects for both biology and society. Several examples are given for further discussion.

Along the Central Dogma-Controlling Gene Expression with Small Molecules.

PubMed

Schneider-Poetsch, Tilman; Yoshida, Minoru

2018-05-04

The central dogma of molecular biology, that DNA is transcribed into RNA and RNA translated into protein, was coined in the early days of modern biology. Back in the 1950s and 1960s, bacterial genetics first opened the way toward understanding life as the genetically encoded interaction of macromolecules. As molecular biology progressed and our knowledge of gene control deepened, it became increasingly clear that expression relied on many more levels of regulation. In the process of dissecting mechanisms of gene expression, specific small-molecule inhibitors played an important role and became valuable tools of investigation. Small molecules offer significant advantages over genetic tools, as they allow inhibiting a process at any desired time point, whereas mutating or altering the gene of an important regulator would likely result in a dead organism. With the advent of modern sequencing technology, it has become possible to monitor global cellular effects of small-molecule treatment and thereby overcome the limitations of classical biochemistry, which usually looks at a biological system in isolation. This review focuses on several molecules, especially natural products, that have played an important role in dissecting gene expression and have opened up new fields of investigation as well as clinical venues for disease treatment. Expected final online publication date for the Annual Review of Biochemistry Volume 87 is June 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Periodontal Ligament Stem Cells: Current Status, Concerns, and Future Prospects

PubMed Central

Zhu, Wenjun; Liang, Min

2015-01-01

Periodontal ligament stem cells (PDLSCs), which reside in the perivascular space of the periodontium, possess characteristics of mesenchymal stem cells and are a promising tool for periodontal regeneration. Recently, great progress has been made in PDLSC transplantation. Investigators are attempting to maximize the proliferation and differentiation potential of PDLSCs by modifying culture conditions and applying growth factors. Nevertheless, problems remain. First, incomparability among different studies must be minimized by establishing standard guidelines for culture and identification of PDLSCs. Notably, attention should be paid to the biological safety of PDLSC transplantation. The present review updates the latest findings regarding PDLSCs and discusses standard criteria for culture and identification of PDLSCs. Finally, the review calls for careful consideration of PDLSC transplantation safety. PMID:25861283

Methods to Assess Mitochondrial Morphology in Mammalian Cells Mounting Autophagic or Mitophagic Responses.

PubMed

Marchi, S; Bonora, M; Patergnani, S; Giorgi, C; Pinton, P

2017-01-01

It is widely acknowledged that mitochondria are highly active structures that rapidly respond to cellular and environmental perturbations by changing their shape, number, and distribution. Mitochondrial remodeling is a key component of diverse biological processes, ranging from cell cycle progression to autophagy. In this chapter, we describe different methodologies for the morphological study of the mitochondrial network. Instructions are given for the preparation of samples for fluorescent microscopy, based on genetically encoded strategies or the employment of synthetic fluorescent dyes. We also propose detailed protocols to analyze mitochondrial morphometric parameters from both three-dimensional and bidimensional datasets. Finally, we describe a protocol for the visualization and quantification of mitochondrial structures through electron microscopy. © 2017 Elsevier Inc. All rights reserved.

Genitals to genes: the history and biology of gender verification in the Olympics.

PubMed

Rupert, James L

2011-01-01

From 1968 to 1998, female Olympic athletes were expected to prove their "femininity," ostensibly to stop male "ringers" from passing themselves off as female competitors. Rumours that men were competing in drag had been around since at least the 1936 games. The sex tests started out as simple anatomical examinations--the "nude parade," but rapidly progressed to cellular-based tests (the presence of a Barr body), and eventually to molecular-based tests (the absence of the SRY gene). Women went from being defined by genitalia to cellular characteristics, and finally, by genotype but ironically, as the tests become more sophisticated, both sensitivity and specificity suffered. This paper reviews the science underlying the sex tests, their history, and the controversy that accompanied them.

Eicosanoid signalling pathways in the development and progression of colorectal cancer: novel approaches for prevention/intervention.

PubMed

Cathcart, Mary-Clare; Lysaght, Joanne; Pidgeon, Graham P

2011-12-01

Arachidonic acid metabolism through cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P-450 epoxygenase (EPOX) pathways leads to the generation of biologically active eicosanoids, including prostanoids, leukotrienes, hydroxyeicosatetraenoic acid, epoxyeicosatrienoic acid and hydroperoxyeicosatetraenoic acids. Eicosanoid expression levels vary during tumor development and progression of a range of malignancies, including colorectal cancer. The actions of these autocoids are also directly influenced by diet, as demonstrated by recent evidence for omega-3 fatty acids in colorectal cancer (CRC) prevention and/or treatment. Eicosanoids regulate CRC development and progression, while inhibition of these pathways has generally been shown to inhibit tumor growth/progression. A progressive sequence of colorectal cancer development has been identified, ranging from normal colon, to colitis, dysplasia, and carcinoma. While both COX and LOX inhibition are both promising candidates for colorectal cancer prevention and/or treatment, there is an urgent need to understand the mechanisms through which these signalling pathways mediate their effects on tumorigenesis. This will allow identification of safer, more effective strategies for colorectal cancer prevention and/or treatment. In particular, binding to/signalling through prostanoid receptors have recently been the subject of considerable interest in this area. In this review, we discuss the role of the eicosanoid signalling pathways in the development and progression of colorectal cancer. We discuss the effects of the eicosanoids on tumor cell proliferation, their roles in cell death induction, effects on angiogenesis, migration, invasion and their regulation of the immune response. Signal transduction pathways involved in these processes are also discussed. Finally, novel approaches targeting these arachidonic acid-derived eicosanoids (using pharmacological or natural agents) for chemoprevention and/or treatment of colorectal cancer are outlined.

Biology Division progress report, October 1, 1993--September 30, 1995

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

NONE

1995-10-01

This Progress Report summarizes the research endeavors of the Biology Division of the Oak Ridge National Laboratory during the period October 1, 1993, through September 30, 1995. The report is structured to provide descriptions of current activities and accomplishments in each of the Division`s major organizational units. Lists of information to convey the entire scope of the Division`s activities are compiled at the end of the report. Attention is focused on the following research activities: molecular, cellular, and cancer biology; mammalian genetics and development; genome mapping program; and educational activities.

Climate Change Effects on Stream and River Biological Indicators: A Preliminary Analysis (Final Report)

EPA Science Inventory

EPA announced the availability of the final report,Climate Change Effects on Stream and River Biological Indicators: A Preliminary Analysis. This report is a preliminary assessment that describes how biological indicators are likely to respond to climate change, how wel...

From Fancy to Reason: Scaling Deaf and Hearing Children’s Understanding of Theory of Mind and Pretence

PubMed Central

Peterson, Candida C.; Wellman, Henry M.

2011-01-01

We examined deaf and hearing children’s progression of steps in theory-of-mind (ToM) development including their understanding of social pretending. Ninety-three children (33 deaf; 60 hearing) aged 3 to 13 years were tested on a set of six closely-matched ToM tasks. Results showed that deaf children were delayed substantially behind hearing children in understanding pretending, false belief and other ToM concepts, in line with their delayed uptake of social pretend play. By using a scaling methodology, we confirmed previous evidence of a consistent five-step developmental progression for both groups. Moreover, by including social pretence understanding, both deaf and hearing children’s ToM sequences were shown to extend reliably to six sequential developmental steps. Finally and focally, even though both groups’ sequences were six steps long, the placement of pretence relative to other ToM milestones varied with hearing status. Deaf children understood social pretending at an earlier step in the ToM sequence than hearing children, albeit at a later chronological age. Theoretically, the findings are relevant to questions about how universal developmental progressions come together along with culturally-distinctive inputs and biological factors (such as hearing loss) to set the pace for ToM development. PMID:19998533

From fancy to reason: scaling deaf and hearing children's understanding of theory of mind and pretence.

PubMed

Peterson, Candida C; Wellman, Henry M

2009-06-01

We examined deaf and hearing children's progression of steps in theory of mind (ToM) development including their understanding of social pretending. Ninety-three children (33 deaf; 60 hearing) aged 3-13 years were tested on a set of six closely matched ToM tasks. Results showed that deaf children were delayed substantially behind hearing children in understanding pretending, false belief (FB) and other ToM concepts, in line with their delayed uptake of social pretend (SP) play. By using a scaling methodology, we confirmed previous evidence of a consistent five-step developmental progression for both groups. Moreover, by including social pretence understanding, both deaf and hearing children's ToM sequences were shown to extend reliably to six sequential developmental steps. Finally and focally, even though both groups' sequences were six steps long, the placement of pretence relative to other ToM milestones varied with hearing status. Deaf children understood social pretending at an earlier step in the ToM sequence than hearing children, albeit at a later chronological age. Theoretically, the findings are relevant to questions about how universal developmental progressions come together along with culturally distinctive inputs and biological factors (such as hearing loss) to set the pace for ToM development.

Final Progress Report for Ionospheric Dusty Plasma In the Laboratory [Smokey Plasma

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

Robertson, Scott

2010-07-31

“Ionospheric Dusty Plasma in the Laboratory” is a research project with the purpose of finding and reproducing the characteristics of plasma in the polar mesosphere that is unusually cold (down to 140 K) and contains nanometer-sized dust particles. This final progress report summarizes results from four years of effort that include a final year with a no-cost extension.

Biomechanics of far cortical locking.

PubMed

Bottlang, Michael; Feist, Florian

2011-02-01

The development of far cortical locking (FCL) was motivated by a conundrum: locked plating constructs provide inherently rigid stabilization, yet they should facilitate biologic fixation and secondary bone healing that relies on flexible fixation to stimulate callus formation. Recent studies have confirmed that the high stiffness of standard locked plating constructs can suppress interfragmentary motion to a level that is insufficient to reliably promote secondary fracture healing by callus formation. Furthermore, rigid locking screws cause an uneven stress distribution that may lead to stress fracture at the end screw and stress shielding under the plate. This review summarizes four key features of FCL constructs that have been shown to enhance fixation and healing of fractures: flexible fixation, load distribution, progressive stiffening, and parallel interfragmentary motion. Specifically, flexible fixation provided by FCL reduces the stiffness of a locked plating construct by 80% to 88% to actively promote callus proliferation similar to an external fixator. Load is evenly distributed between FCL screws to mitigate stress risers at the end screw. Progressive stiffening occurs by near cortex support of FCL screws and provides additional support under elevated loading. Finally, parallel interfragmentary motion by the S-shaped flexion of FCL screws promotes symmetric callus formation. In combination, these features of FCL constructs have been shown to induce more callus and to yield significantly stronger and more consistent healing compared with standard locked plating constructs. As such, FCL constructs function as true internal fixators by replicating the biomechanical behavior and biologic healing response of external fixators.

Biomechanics of Far Cortical Locking

PubMed Central

Bottlang, Michael; Feist, Florian

2011-01-01

The development of FCL was motivated by a conundrum: locked plating constructs provide inherently rigid stabilization, yet they should facilitate biological fixation and secondary bone healing that relies on flexible fixation to stimulate callus formation. Recent studies have confirmed that the high stiffness of standard locked plating constructs can suppress interfragmentary motion to a level that is insufficient to reliably promote secondary fracture healing by callus formation. Furthermore, rigid locking screws cause an uneven stress distribution that may lead to stress fracture at the end screw and stress shielding under the plate. This review summarizes four key features of FCL constructs that have shown to enhance fixation and fracture healing: Flexible fixation, load distribution, progressive stiffening, and parallel interfragmentary motion. Specifically, flexible fixation provided by FCL reduces the stiffness of a locked plating construct by 80–88% to actively promote callus proliferation similar to an external fixator. Load distribution is evenly shared between FCL screws to mitigate stress risers at the end screw. Progressive stiffening occurs by near cortex support of FCL screws and provides additional support under elevated loading. Finally, parallel interfragmentary motion by s-shaped flexion of FCL screws has shown to induce symmetric callus formation. In combination, these features of FCL constructs have shown to induce more callus and to yield significantly stronger and more consistent healing compared to standard locked plating constructs. As such, FCL constructs function as true internal fixators by replicating the biomechanical behavior and biological healing response of external fixators. PMID:21248556

New-onset vitiligo and progression of pre-existing vitiligo during treatment with biological agents in chronic inflammatory diseases.

PubMed

Méry-Bossard, L; Bagny, K; Chaby, G; Khemis, A; Maccari, F; Marotte, H; Perrot, J L; Reguiai, Z; Sigal, M L; Avenel-Audran, M; Boyé, T; Grasland, A; Gillard, J; Jullien, D; Toussirot, E

2017-01-01

The development of vitiligo during treatment with biological agents is an unusual event and only a few isolated cases have been reported. To describe the clinical characteristics and evolution of patients developing new-onset vitiligo following initiation of a biological agent for chronic inflammatory disease; and also to report the clinical course of pre-existing vitiligo under biological therapy. This nationwide multicentre, retrospective study, carried out between July 2013 and January 2015, describes the characteristics of a large series of 18 patients (psoriasis N = 8, inflammatory rheumatic diseases N = 8, ulcerative colitis N = 1, uveitis N = 1) who developed new-onset vitiligo while receiving a biological agent. TNFα inhibitors were the most common biological agent involved (13/18) while anti-IL-12/23 and anti-IL-17 agents or abatacept were less common (4/18 and 1/18 respectively). Mean duration of biological agent exposure before vitiligo onset was 13.9 ± 16.5 months. Outcome was favourable for most patients (15/17) while maintaining the biological agent. Data were also collected for 18 patients (psoriasis N = 5, inflammatory rheumatic diseases N = 10, inflammatory bowel diseases N = 2, SAPHO N = 1) who had pre-existing vitiligo when treatment with a biological agent started (TNFα inhibitors N = 15, ustekinumab N = 1, rituximab N = 1, tocilizumab N = 1). Vitiligo progressed in seven patients and was stable or improved in eight cases. Vitiligo may thus emerge and/or progress during treatment with various biological agents, mainly TNFα inhibitors and could be a new paradoxical skin reaction. De novo vitiligo displays a favourable outcome when maintaining the biological agent, whereas the prognosis seems worse in cases of pre-existing vitiligo. © 2016 European Academy of Dermatology and Venereology.

A Consumer's Guide to Biology Textbooks 1985.

ERIC Educational Resources Information Center

Moyer, Wayne A.; Mayer, William V.

Presented are critical reviews of 18 biology textbooks submitted for consideration by the Texas State Board of Education during 1984. These reviews are provided in three categories: (1) general biology textbooks: "Biology and Human Progress"--Prentice Hall; "Scott, Foresman Life Science"--Scott, Foresman; "Living Things"--Holt, Rinehart, and…

Boron-doped diamond nano/microelectrodes for biosensing and in vitro measurements.

PubMed

Dong, Hua; Wang, Shihua; Galligan, James J; Swain, Greg M

2011-01-01

Since the fabrication of the first diamond electrode in the mid 1980s, repid progress has been made on the development and application of this new type of electrode material. Boron-doped diamond (BDD) electrodes exhibit outstanding properties compared to oxygen-containing sp2 carbon electrodes. These properties make BDD electrodes an ideal choice for use in complex samples. In recent years, BDD microelectrodes have been applied to in vitro measurements of biological molecules in tissues and cells. This review will summarize recent progress in the development and applications of BDD electrodes in bio-sensing and in vitro measurements of biomolecules. In the first section, the methods for BDD diamond film deposition and BDD microelectrodes preparation are described. This is followed by a description and discussion of several approaches for characterization of the BDD electrode surface structure, morphology, and electrochemical activity. Further, application of BDD microelectrodes for use in the in vitro analysis of norepinephrine (NE), serotonin (5-HT), nitric oxide (NO), histamine, and adenosine from tissues are summarized and finally some of the remaining challenges are discussed.

MicroRNAs in right ventricular remodelling.

PubMed

Batkai, Sandor; Bär, Christian; Thum, Thomas

2017-10-01

Right ventricular (RV) remodelling is a lesser understood process of the chronic, progressive transformation of the RV structure leading to reduced functional capacity and subsequent failure. Besides conditions concerning whole hearts, some pathology selectively affects the RV, leading to a distinct RV-specific clinical phenotype. MicroRNAs have been identified as key regulators of biological processes that drive the progression of chronic diseases. The role of microRNAs in diseases affecting the left ventricle has been studied for many years, however there is still limited information on microRNAs specific to diseases in the right ventricle. Here, we review recently described details on the expression, regulation, and function of microRNAs in the pathological remodelling of the right heart. Recently identified strategies using microRNAs as pharmacological targets or biomarkers will be highlighted. Increasing knowledge of pathogenic microRNAs will finally help improve our understanding of underlying distinct mechanisms and help utilize novel targets or biomarkers to develop treatments for patients suffering from right heart diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Progress towards biocompatible intracortical microelectrodes for neural interfacing applications

NASA Astrophysics Data System (ADS)

Jorfi, Mehdi; Skousen, John L.; Weder, Christoph; Capadona, Jeffrey R.

2015-02-01

To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing.

Progress Towards Biocompatible Intracortical Microelectrodes for Neural Interfacing Applications

PubMed Central

Jorfi, Mehdi; Skousen, John L.; Weder, Christoph; Capadona, Jeffrey R.

2015-01-01

To ensure long-term consistent neural recordings, next-generation intracortical microelectrodes are being developed with an increased emphasis on reducing the neuro-inflammatory response. The increased emphasis stems from the improved understanding of the multifaceted role that inflammation may play in disrupting both biologic and abiologic components of the overall neural interface circuit. To combat neuro-inflammation and improve recording quality, the field is actively progressing from traditional inorganic materials towards approaches that either minimizes the microelectrode footprint or that incorporate compliant materials, bioactive molecules, conducting polymers or nanomaterials. However, the immune-privileged cortical tissue introduces an added complexity compared to other biomedical applications that remains to be fully understood. This review provides a comprehensive reflection on the current understanding of the key failure modes that may impact intracortical microelectrode performance. In addition, a detailed overview of the current status of various materials-based approaches that have gained interest for neural interfacing applications is presented, and key challenges that remain to be overcome are discussed. Finally, we present our vision on the future directions of materials-based treatments to improve intracortical microelectrodes for neural interfacing. PMID:25460808

Boron-doped diamond nano/microelectrodes for bio-sensing and in vitro measurements

PubMed Central

Dong, Hua; Wang, Shihua; Galligan, James J.; Swain, Greg M.

2015-01-01

Since the fabrication of the first diamond electrode in the mid 1980s, repid progress has been made on the development and application of this new type of electrode material. Boron-doped diamond (BDD) electrodes exhibit outstanding properties compared to oxygen-containing sp2 carbon electrodes. These properties make BDD electrodes an ideal choice for use in complex samples. In recent years, BDD microelectrodes have been applied to in vitro and in vivo measurements of biological molecules in animals, tissues and cells. This review will summarize recent progress in the development and applications of BDD electrodes in bio-sensing and in vitro measurements of biomolecules. In the first section, the methods for BDD nanocrystalline diamond film deposition and BDD microelectrodes preparation are described. This is followed by a description and discussion of several approaches for characterization of the BDD electrode surface structure, morphology, and electrochemical activity. Further, application of BDD microelectrodes for use in the in vitro analysis of norepinephrine (NE), serotonin (5-HT), nitric oxide (NO), histamine, and adenosine from tissues are summarized and finally some of the remaining challenges are discussed. PMID:21196394

New Horizons and New Strategies in Arms Control

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

Brown, J. editor

In the last ten years, since the break-up of the Soviet Union, remarkable progress in arms control and disarmament has occurred. The Nuclear Non-Proliferation Treaty (NPT), the completion of the Comprehensive Test Ban Treaty (CTBT), and the Chemical Weapons Treaty (CWC) are indicative of the great strides made in the non- proliferation arena. Simultaneously, the Intermediate Nuclear Forces Treaty (INF), the Conventional Forces Treaty in Europe (CFE), and the Strategic Arms Reduction Treaties (START), all associated with US-Soviet Union (now Russia) relations have assisted in redefining European relations and the security landscape. Finally, it now appears that progress is inmore » the offing in developing enhanced compliance measures for the Biological and Toxin Weapons Convention (BTWC). In sum, all of these achievements have set the stage for the next round of arms control activities, which may lead to a much broader, and perhaps more diffused multilateral agenda. In this new and somewhat unpredictable international setting, arms control and disarmament issues will require solutions that are both more creative and innovative than heretofore.« less

Single molecule microscopy in 3D cell cultures and tissues.

PubMed

Lauer, Florian M; Kaemmerer, Elke; Meckel, Tobias

2014-12-15

From the onset of the first microscopic visualization of single fluorescent molecules in living cells at the beginning of this century, to the present, almost routine application of single molecule microscopy, the method has well-proven its ability to contribute unmatched detailed insight into the heterogeneous and dynamic molecular world life is composed of. Except for investigations on bacteria and yeast, almost the entire story of success is based on studies on adherent mammalian 2D cell cultures. However, despite this continuous progress, the technique was not able to keep pace with the move of the cell biology community to adapt 3D cell culture models for basic research, regenerative medicine, or drug development and screening. In this review, we will summarize the progress, which only recently allowed for the application of single molecule microscopy to 3D cell systems and give an overview of the technical advances that led to it. While initially posing a challenge, we finally conclude that relevant 3D cell models will become an integral part of the on-going success of single molecule microscopy. Copyright © 2014 Elsevier B.V. All rights reserved.

Quantitative biological surface science: challenges and recent advances.

PubMed

Höök, Fredrik; Kasemo, Bengt; Grunze, Michael; Zauscher, Stefan

2008-12-23

Biological surface science is a broad, interdisciplinary subfield of surface science, where properties and processes at biological and synthetic surfaces and interfaces are investigated, and where biofunctional surfaces are fabricated. The need to study and to understand biological surfaces and interfaces in liquid environments provides sizable challenges as well as fascinating opportunities. Here, we report on recent progress in biological surface science that was described within the program assembled by the Biomaterial Interface Division of the Science and Technology of Materials, Interfaces and Processes (www.avs.org) during their 55th International Symposium and Exhibition held in Boston, October 19-24, 2008. The selected examples show that the rapid progress in nanoscience and nanotechnology, hand-in-hand with theory and simulation, provides increasingly sophisticated methods and tools to unravel the mechanisms and details of complex processes at biological surfaces and in-depth understanding of biomolecular surface interactions.

Organic Chemistry and Biology: Chemical Biology Through the Eyes of Collaboration

PubMed Central

Hruby, Victor J.

2011-01-01

From a scientific perspective, efforts to understand biology including what constitutes health and disease has become a chemical problem. However, chemists and biologists “see” the problems of understanding biology from different perspectives, and this has retarded progress in solving the problems especially as they relate to health and disease. This suggests that close collaboration between chemists and biologists is not only necessary but essential for progress in both the biology and chemistry that will provide solutions to the global questions of biology. This perspective has directed my scientific efforts for the past 45 years, and in this overview I provide my perspective of how the applications of synthetic chemistry, structural design, and numerous other chemical principles have intersected in my collaborations with biologists to provide new tools, new science, and new insights that were only made possible and fruitful by these collaborations. PMID:20000552

Role of Forkhead Box Class O proteins in cancer progression and metastasis.

PubMed

Kim, Chang Geun; Lee, Hyemin; Gupta, Nehal; Ramachandran, Sharavan; Kaushik, Itishree; Srivastava, Sangeeta; Kim, Sung-Hoon; Srivastava, Sanjay K

2018-06-01

It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3 K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far. Thus, with previous experimental evidences, the present review discussed the role of FoxOs in association with metastasis related molecules including cannabinoid receptor 1 (CNR1), Cdc25A/Cdk2, Src, serum and glucocorticoid inducible kinases (SGKs), CXCR4, E-cadherin, annexin A8 (ANXA8), Zinc finger E-box-binding homeobox 2 (ZEB2), human epidermal growth factor receptor 2 (HER2) and mRNAs such as miR-182, miR-135b, miR-499-5p, miR-1274a, miR-150, miR-34b/c and miR-622, subsequently analyzed the molecular mechanism of some natural compounds targeting FoxOs and finally suggested future research directions in cancer progression and metastasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chance, purpose, and progress in evolution and christianity.

PubMed

Mix, Lucas J; Masel, Joanna

2014-08-01

Evolutionary biology has a complex relationship with ideas of chance, purpose, and progress. Probability plays a subtle role; strikingly, founding figures in statistics were motivated by evolutionary questions. The findings of evolutionary biology have been used both in support of narratives of progress, and in their deconstruction. Likewise, professional biologists bring to their scientific work a set of preconceptions about chance and progress, grounded in their philosophical, religious, and/or political views. From the religious side, questions of purpose are ever-present. We explore this interplay in five broad categories: chance, progress, intelligence, eugenics, and the evolution of religious practices, each the subject of a semester long symposium. The intellectual influence of evolutionary biology has had a broad societal impact in these areas. Based on our experience, we draw attention to a number of relevant facts that, while accepted by experts in their respective fields, may be unfamiliar outside them. We list common areas of miscommunication, including specific examples and discussing causes: sometimes semantics and sometimes more substantive knowledge barriers. We also make recommendations for those attempting similar dialogue. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Imaging Cellular Architecture with X-rays

PubMed Central

Larabell, Carolyn A.; Nugent, Keith A.

2012-01-01

X-ray imaging of biological samples is progressing rapidly. In this paper we review the progress to date in high resolution imaging of cellular architecture. In particular we survey the progress in soft X-ray tomography and argue that the field is coming of age and that important biological insights are starting to emerge. We then review the new ideas based on coherent diffraction. These methods are at a much earlier stage of development but, as they eliminate the need for X-ray optics, have the capacity to provide substantially better spatial resolution than zone plate based methods. PMID:20869868

Development of the Biology Card Sorting Task to Measure Conceptual Expertise in Biology

ERIC Educational Resources Information Center

Smith, Julia I.; Combs, Elijah D.; Nagami, Paul H.; Alto, Valerie M.; Goh, Henry G.; Gourdet, Muryam A. A.; Hough, Christina M.; Nickell, Ashley E.; Peer, Adrian G.; Coley, John D.; Tanner, Kimberly D.

2013-01-01

There are widespread aspirations to focus undergraduate biology education on teaching students to think conceptually like biologists; however, there is a dearth of assessment tools designed to measure progress from novice to expert biological conceptual thinking. We present the development of a novel assessment tool, the Biology Card Sorting Task,…

PSI-Center Final Progress Report

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

Jarboe, Thomas R.; Shumlak, Uri; Sovinec, Carl

This is the Final Progress Report of the Plasma Science and Innovation Center (PSI-Center) covering March 2014 through February 2017. The Center has accomplished a great deal during this period. The PSI-Center is organized into four groups: Edge and Dynamic Neutrals; Transport and Kinetic Effects; Equilibrium, Stability, and Kinetic Effects in 3D Topologies; and Interface for Validation. Each group has made good progress and the results from each group are given in detail.

Bending Genders: The Biology of Natural Sex Change in Fish.

PubMed

Todd, Erica V; Liu, Hui; Muncaster, Simon; Gemmell, Neil J

2016-01-01

Sexual fate is no longer seen as an irreversible deterministic switch set during early embryonic development but as an ongoing battle for primacy between male and female developmental trajectories. That sexual fate is not final and must be actively maintained via continuous suppression of the opposing sexual network creates the potential for flexibility into adulthood. In many fishes, sexuality is not only extremely plastic, but sex change is a usual and adaptive part of the life cycle. Sequential hermaphrodites begin life as one sex, changing sometime later to the other, and include species capable of protandrous (male-to-female), protogynous (female-to-male), or serial (bidirectional) sex change. Natural sex change involves coordinated transformations across multiple biological systems, including behavioural, anatomical, neuroendocrine, and molecular axes. We here review the biological processes underlying this amazing transformation, focussing particularly on its molecular basis, which remains poorly understood, but where new genomic technologies are significantly advancing our understanding of how sex change is initiated and progressed at the molecular level. Knowledge of how a usually committed developmental process remains plastic in sequentially hermaphroditic fishes is relevant to understanding the evolution and functioning of sexual developmental systems in vertebrates generally, as well as pathologies of sexual development in humans. © 2016 S. Karger AG, Basel.

Recent Advances on Neuromorphic Systems Using Phase-Change Materials

NASA Astrophysics Data System (ADS)

Wang, Lei; Lu, Shu-Ren; Wen, Jing

2017-05-01

Realization of brain-like computer has always been human's ultimate dream. Today, the possibility of having this dream come true has been significantly boosted due to the advent of several emerging non-volatile memory devices. Within these innovative technologies, phase-change memory device has been commonly regarded as the most promising candidate to imitate the biological brain, owing to its excellent scalability, fast switching speed, and low energy consumption. In this context, a detailed review concerning the physical principles of the neuromorphic circuit using phase-change materials as well as a comprehensive introduction of the currently available phase-change neuromorphic prototypes becomes imperative for scientists to continuously progress the technology of artificial neural networks. In this paper, we first present the biological mechanism of human brain, followed by a brief discussion about physical properties of phase-change materials that recently receive a widespread application on non-volatile memory field. We then survey recent research on different types of neuromorphic circuits using phase-change materials in terms of their respective geometrical architecture and physical schemes to reproduce the biological events of human brain, in particular for spike-time-dependent plasticity. The relevant virtues and limitations of these devices are also evaluated. Finally, the future prospect of the neuromorphic circuit based on phase-change technologies is envisioned.

Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism.

PubMed

Palczewski, Grzegorz; Widjaja-Adhi, M Airanthi K; Amengual, Jaume; Golczak, Marcin; von Lintig, Johannes

2016-09-01

Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health. However, knowledge about their biological action and the consequences of their dietary accumulation in mammals is limited. Progress in this research field is limited by the expeditious metabolism of carotenoids in rodents and the confounding production of apocarotenoid signaling molecules. Herein, we established a mouse model lacking the enzymes responsible for carotenoid catabolism and apocarotenoid production, fed on either a β-carotene- or a zeaxanthin-enriched diet. Applying a genome wide microarray analysis, we assessed the effects of the parent carotenoids on the liver transcriptome. Our analysis documented changes in pathways for liver lipid metabolism and mitochondrial respiration. We biochemically defined these effects, and observed that β-carotene accumulation resulted in an elevation of liver triglycerides and liver cholesterol, while zeaxanthin accumulation increased serum cholesterol levels. We further show that carotenoids were predominantly transported within HDL particles in the serum of mice. Finally, we provide evidence that carotenoid accumulation influenced whole-body respiration and energy expenditure. Thus, we observed that accumulation of parent carotenoids interacts with lipid metabolism and that structurally related carotenoids display distinct biological functions in mammals. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Antibiotics with anaerobic ammonium oxidation in urban wastewater treatment

NASA Astrophysics Data System (ADS)

Zhou, Ruipeng; Yang, Yuanming

2017-05-01

Biofilter process is based on biological oxidation process on the introduction of fast water filter design ideas generated by an integrated filtration, adsorption and biological role of aerobic wastewater treatment process various purification processes. By engineering example, we show that the process is an ideal sewage and industrial wastewater treatment process of low concentration. Anaerobic ammonia oxidation process because of its advantage of the high efficiency and low consumption, wastewater biological denitrification field has broad application prospects. The process in practical wastewater treatment at home and abroad has become a hot spot. In this paper, anammox bacteria habitats and species diversity, and anaerobic ammonium oxidation process in the form of diversity, and one and split the process operating conditions are compared, focusing on a review of the anammox process technology various types of wastewater laboratory research and engineering applications, including general water quality and pressure filtrate sludge digestion, landfill leachate, aquaculture wastewater, monosodium glutamate wastewater, wastewater, sewage, fecal sewage, waste water salinity wastewater characteristics, research progress and application of the obstacles. Finally, we summarize the anaerobic ammonium oxidation process potential problems during the processing of the actual waste water, and proposed future research focus on in-depth study of water quality anammox obstacle factor and its regulatory policy, and vigorously develop on this basis, and combined process optimization.

Recent Advances on Neuromorphic Systems Using Phase-Change Materials.

PubMed

Wang, Lei; Lu, Shu-Ren; Wen, Jing

2017-12-01

Realization of brain-like computer has always been human's ultimate dream. Today, the possibility of having this dream come true has been significantly boosted due to the advent of several emerging non-volatile memory devices. Within these innovative technologies, phase-change memory device has been commonly regarded as the most promising candidate to imitate the biological brain, owing to its excellent scalability, fast switching speed, and low energy consumption. In this context, a detailed review concerning the physical principles of the neuromorphic circuit using phase-change materials as well as a comprehensive introduction of the currently available phase-change neuromorphic prototypes becomes imperative for scientists to continuously progress the technology of artificial neural networks. In this paper, we first present the biological mechanism of human brain, followed by a brief discussion about physical properties of phase-change materials that recently receive a widespread application on non-volatile memory field. We then survey recent research on different types of neuromorphic circuits using phase-change materials in terms of their respective geometrical architecture and physical schemes to reproduce the biological events of human brain, in particular for spike-time-dependent plasticity. The relevant virtues and limitations of these devices are also evaluated. Finally, the future prospect of the neuromorphic circuit based on phase-change technologies is envisioned.

Paradigms and progress in vocal fold restoration.

PubMed

Ford, Charles N

2008-09-01

Science advances occur through orderly steps, puzzle-solving leaps, or divergences from the accepted disciplinary matrix that occasionally result in a revolutionary paradigm shift. Key advances must overcome bias, criticism, and rejection. Examples in biological science include use of embryonic stem cells, recognition of Helicobacter pylori in the etiology of ulcer disease, and the evolution of species. Our work in vocal fold restoration reflects these patterns. We progressed through phases of tissue replacement with fillers and biological implants, to current efforts at vocal fold regeneration through tissue engineering, and face challenges of a new "systems biology" paradigm embracing genomics and proteomics.

Construction and analysis of lncRNA-lncRNA synergistic networks to reveal clinically relevant lncRNAs in cancer.

PubMed

Li, Yongsheng; Chen, Juan; Zhang, Jinwen; Wang, Zishan; Shao, Tingting; Jiang, Chunjie; Xu, Juan; Li, Xia

2015-09-22

Long non-coding RNAs (lncRNAs) play key roles in diverse biological processes. Moreover, the development and progression of cancer often involves the combined actions of several lncRNAs. Here we propose a multi-step method for constructing lncRNA-lncRNA functional synergistic networks (LFSNs) through co-regulation of functional modules having three features: common coexpressed genes of lncRNA pairs, enrichment in the same functional category and close proximity within protein interaction networks. Applied to three cancers, we constructed cancer-specific LFSNs and found that they exhibit a scale free and modular architecture. In addition, cancer-associated lncRNAs tend to be hubs and are enriched within modules. Although there is little synergistic pairing of lncRNAs across cancers, lncRNA pairs involved in the same cancer hallmarks by regulating same or different biological processes. Finally, we identify prognostic biomarkers within cancer lncRNA expression datasets using modules derived from LFSNs. In summary, this proof-of-principle study indicates synergistic lncRNA pairs can be identified through integrative analysis of genome-wide expression data sets and functional information.

Expression, production, and renaturation of a functional single-chain variable antibody fragment (scFv) against human ICAM-1

PubMed Central

Sun, H.; Wu, G.M.; Chen, Y.Y.; Tian, Y.; Yue, Y.H.; Zhang, G.L.

2014-01-01

Intercellular adhesion molecule-1 (ICAM-1) is an important factor in the progression of inflammatory responses in vivo. To develop a new anti-inflammatory drug to block the biological activity of ICAM-1, we produced a monoclonal antibody (Ka=4.19×10−8 M) against human ICAM-1. The anti-ICAM-1 single-chain variable antibody fragment (scFv) was expressed at a high level as inclusion bodies in Escherichia coli. We refolded the scFv (Ka=2.35×10−7 M) by ion-exchange chromatography, dialysis, and dilution. The results showed that column chromatography refolding by high-performance Q Sepharose had remarkable advantages over conventional dilution and dialysis methods. Furthermore, the anti-ICAM-1 scFv yield of about 60 mg/L was higher with this method. The purity of the final product was greater than 90%, as shown by denaturing gel electrophoresis. Enzyme-linked immunosorbent assay, cell culture, and animal experiments were used to assess the immunological properties and biological activities of the renatured scFv. PMID:24919171

Facing the challenges of multiscale modelling of bacterial and fungal pathogen–host interactions

PubMed Central

Schleicher, Jana; Conrad, Theresia; Gustafsson, Mika; Cedersund, Gunnar; Guthke, Reinhard

2017-01-01

Abstract Recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. At the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. Using such models, hypotheses can systematically be tested. In this review, we present state-of-the-art multiscale modelling of bacterial and fungal infections, considering both the pathogen and host as well as their interaction. Multiscale modelling of the interactions of bacteria, especially Mycobacterium tuberculosis, with the human host is quite advanced. In contrast, models for fungal infections are still in their infancy, in particular regarding infections with the most important human pathogenic fungi, Candida albicans and Aspergillus fumigatus. We reflect on the current availability of computational approaches for multiscale modelling of host–pathogen interactions and point out current challenges. Finally, we provide an outlook for future requirements of multiscale modelling. PMID:26857943

Recent advances in metastasis research.

PubMed

Molloy, Tim; van 't Veer, Laura J

2008-02-01

Advances in the early prediction, detection, and treatment of metastatic disease has improved the outlook in cancer patients in recent decades, however, metastasis remains the major cause of death in affected individuals. Metastasis occurs in a series of discreet biological steps in which a single, frequently clinically occult micrometastatic cell travels from the primary tumor to a distant location, where it lodges, grows, and ultimately results in the patient's death. Recent work has provided many new insights in the mechanisms and biology behind metastatic spread. This short review surveys some of the most important recent developments that have helped increase our understanding of the three broad phases of metastasis - the genesis of the metastatic cell through the loss of local constraints in the primary tumor microenvironment, dissemination of the cell to a distant organ while avoiding immune surveillance, and finally lodging and growth of the overt metastasis. These studies are providing mounting evidence that the interactions between tumor and normal cells and tissues are critical for disease progression - a paradigm that will provide a fertile area for future research.

Carbon budgets of biological soil crusts at micro-, meso-, and global scales

USGS Publications Warehouse

Sancho, Leopoldo G; Belnap, Jayne; Colesie, Claudia; Raggio, Jose; Weber, Bettina

2016-01-01

The importance of biocrusts in the ecology of arid lands across all continents is widely recognized. In spite of this broad distribution, contributions of biocrusts to the global biogeochemical cycles have only recently been considered. While these studies opened a new view on the global role of biocrusts, they also clearly revealed the lack of data for many habitats and of overall standards for measurements and analysis. In order to understand carbon cycling in biocrusts and the progress which has been made during the last 15 years, we offer a multi-scale approach covering different climatic regions. We also include a discussion on available measurement techniques at each scale: A micro-scale section focuses on the individual organism level, including modeling based on the combination of field and lab data. The meso-scale section addresses the CO2 exchange of a complete ecosystem or at the community level. Finally, we consider the contribution of biocrusts at a global scale, giving a general perspective of the most relevant findings regarding the role of biological soil crusts in the global terrestrial carbon cycle.

Development and application of biological technologies in fish genetic breeding.

PubMed

Xu, Kang; Duan, Wei; Xiao, Jun; Tao, Min; Zhang, Chun; Liu, Yun; Liu, ShaoJun

2015-02-01

Fish genetic breeding is a process that remolds heritable traits to obtain neotype and improved varieties. For the purpose of genetic improvement, researchers can select for desirable genetic traits, integrate a suite of traits from different donors, or alter the innate genetic traits of a species. These improved varieties have, in many cases, facilitated the development of the aquaculture industry by lowering costs and increasing both quality and yield. In this review, we present the pertinent literatures and summarize the biological bases and application of selection breeding technologies (containing traditional selective breeding, molecular marker-assisted breeding, genome-wide selective breeding and breeding by controlling single-sex groups), integration breeding technologies (containing cross breeding, nuclear transplantation, germline stem cells and germ cells transplantation, artificial gynogenesis, artificial androgenesis and polyploid breeding) and modification breeding technologies (represented by transgenic breeding) in fish genetic breeding. Additionally, we discuss the progress our laboratory has made in the field of chromosomal ploidy breeding of fish, including distant hybridization, gynogenesis, and androgenesis. Finally, we systematically summarize the research status and known problems associated with each technology.

Tinnitus: pathology of synaptic plasticity at the cellular and system levels

PubMed Central

Guitton, Matthieu J.

2012-01-01

Despite being more and more common, and having a high impact on the quality of life of sufferers, tinnitus does not yet have a cure. This has been mostly the result of limited knowledge of the biological mechanisms underlying this adverse pathology. However, the last decade has witnessed tremendous progress in our understanding on the pathophysiology of tinnitus. Animal models have demonstrated that tinnitus is a pathology of neural plasticity, and has two main components: a molecular, peripheral component related to the initiation phase of tinnitus; and a system-level, central component-related to the long-term maintenance of tinnitus. Using the most recent experimental data and the molecular/system dichotomy as a framework, we describe here the biological basis of tinnitus. We then discuss these mechanisms from an evolutionary perspective, highlighting similarities with memory. Finally, we consider how these discoveries can translate into therapies, and we suggest operative strategies to design new and effective combined therapeutic solutions using both pharmacological (local and systemic) and behavioral tools (e.g., using tele-medicine and virtual reality settings). PMID:22408611

Human Induced Pluripotent Stem Cell-Derived Macrophages for Unraveling Human Macrophage Biology.

PubMed

Zhang, Hanrui; Reilly, Muredach P

2017-11-01

Despite a substantial appreciation for the critical role of macrophages in cardiometabolic diseases, understanding of human macrophage biology has been hampered by the lack of reliable and scalable models for cellular and genetic studies. Human induced pluripotent stem cell (iPSC)-derived macrophages (IPSDM), as an unlimited source of subject genotype-specific cells, will undoubtedly play an important role in advancing our understanding of the role of macrophages in human diseases. In this review, we summarize current literature in the differentiation and characterization of IPSDM at phenotypic, functional, and transcriptomic levels. We emphasize the progress in differentiating iPSC to tissue resident macrophages, and in understanding the ontogeny of in vitro differentiated IPSDM that resembles primitive hematopoiesis, rather than adult definitive hematopoiesis. We review the application of IPSDM in modeling both Mendelian genetic disorders and host-pathogen interactions. Finally, we highlighted the potential areas of research using IPSDM in functional validation of coronary artery disease loci in genome-wide association studies, functional genomic analyses, drug testing, and cell therapeutics in cardiovascular diseases. © 2017 American Heart Association, Inc.

Biology Division progress report, October 1, 1991--September 30, 1993

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

Hartman, F.C.; Cook, J.S.

This Progress Report summarizes the research endeavors of the Biology Division of the Oak Ridge National Laboratory during the period October 1, 1991, through September 30, 1993. The report is structured to provide descriptions of current activities and accomplishments in each of the Division`s major organizational units. Lists of information to convey the entire scope of the Division`s activities are compiled at the end of the report.

Verbal Final Exam in Introductory Biology Yields Gains in Student Content Knowledge and Longitudinal Performance

ERIC Educational Resources Information Center

Luckie, Douglas B.; Rivkin, Aaron M.; Aubry, Jacob R.; Marengo, Benjamin J.; Creech, Leah R.; Sweeder, Ryan D.

2013-01-01

We studied gains in student learning over eight semesters in which an introductory biology course curriculum was changed to include optional verbal final exams (VFs). Students could opt to demonstrate their mastery of course material via structured oral exams with the professor. In a quantitative assessment of cell biology content knowledge,…

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

Research Results Ultra-fast Energy Transfer from Monomer to Dimer within a Trimeric Molecule New Progress in Heterogeneous Catalysis Research Key Progress in Research on Terrestrial Carbon Cycle in China A New Progress in Research on the Mechanism of Bio-Invasion New Findings in Anti-viral infection and Control of Inflammation Major Headway in Avian Origin Research New Progress in Gold-Nanoparticle-Based Biochips Topological Insulator Research Made Important Progress Major Progress in Biodiversity Achieved New Developments of Direct Methods in Protein Crystallography Major Progress in China-UK Collaboration on the Causal Relationship between Volcanic Activity and Biological Distinction News in Brief: NSFC set up "Research Fund for Young Foreign Scholars" How Often Does Human DNA Mutate? Research Progress on Colossal Anisotropic Magneto Resistive Effect

NASA Astrophysics Data System (ADS)

2009-01-01

Ultra-fast Energy Transfer from Monomer to Dimer within a Trimeric Molecule New Progress in Heterogeneous Catalysis Research Key Progress in Research on Terrestrial Carbon Cycle in China A New Progress in Research on the Mechanism of Bio-Invasion New Findings in Anti-viral infection and Control of Inflammation Major Headway in Avian Origin Research New Progress in Gold-Nanoparticle-Based Biochips Topological Insulator Research Made Important Progress Major Progress in Biodiversity Achieved New Developments of Direct Methods in Protein Crystallography Major Progress in China-UK Collaboration on the Causal Relationship between Volcanic Activity and Biological Distinction News in Brief: NSFC set up "Research Fund for Young Foreign Scholars" How Often Does Human DNA Mutate? Research Progress on Colossal Anisotropic Magneto Resistive Effect

How cancer cells dictate their microenvironment: present roles of extracellular vesicles.

PubMed

Naito, Yutaka; Yoshioka, Yusuke; Yamamoto, Yusuke; Ochiya, Takahiro

2017-02-01

Intercellular communication plays an important role in cancer initiation and progression through secretory molecules, including growth factors and cytokines. Recent advances have revealed that small membrane vesicles, termed extracellular vesicles (EVs), served as a regulatory agent in the intercellular communication of cancer. EVs enable the transfer of functional molecules, including proteins, mRNA and microRNAs (miRNAs), into recipient cells. Cancer cells utilize EVs to dictate the unique phenotype of surrounding cells, thereby promoting cancer progression. Against such "education" by cancer cells, non-tumoral cells suppress cancer initiation and progression via EVs. Therefore, researchers consider EVs to be important cues to clarify the molecular mechanisms of cancer biology. Understanding the functions of EVs in cancer progression is an important aspect of cancer biology that has not been previously elucidated. In this review, we summarize experimental data that indicate the pivotal roles of EVs in cancer progression.

Epigenetic Regulation in Prostate Cancer Progression.

PubMed

Ruggero, Katia; Farran-Matas, Sonia; Martinez-Tebar, Adrian; Aytes, Alvaro

2018-01-01

An important number of newly identified molecular alterations in prostate cancer affect gene encoding master regulators of chromatin biology epigenetic regulation. This review will provide an updated view of the key epigenetic mechanisms underlying prostate cancer progression, therapy resistance, and potential actionable mechanisms and biomarkers. Key players in chromatin biology and epigenetic master regulators has been recently described to be crucially altered in metastatic CRPC and tumors that progress to AR independency. As such, epigenetic dysregulation represents a driving mechanism in the reprograming of prostate cancer cells as they lose AR-imposed identity. Chromatin integrity and accessibility for transcriptional regulation are key features altered in cancer progression, and particularly relevant in nuclear hormone receptor-driven tumors like prostate cancer. Understanding how chromatin remodeling dictates prostate development and how its deregulation contributes to prostate cancer onset and progression may improve risk stratification and treatment selection for prostate cancer patients.

Synthetic Genomics and Synthetic Biology Applications Between Hopes and Concerns

PubMed Central

König, Harald; Frank, Daniel; Heil, Reinhard; Coenen, Christopher

2013-01-01

New organisms and biological systems designed to satisfy human needs are among the aims of synthetic genomics and synthetic biology. Synthetic biology seeks to model and construct biological components, functions and organisms that do not exist in nature or to redesign existing biological systems to perform new functions. Synthetic genomics, on the other hand, encompasses technologies for the generation of chemically-synthesized whole genomes or larger parts of genomes, allowing to simultaneously engineer a myriad of changes to the genetic material of organisms. Engineering complex functions or new organisms in synthetic biology are thus progressively becoming dependent on and converging with synthetic genomics. While applications from both areas have been predicted to offer great benefits by making possible new drugs, renewable chemicals or clean energy, they have also given rise to concerns about new safety, environmental and socio-economic risks – stirring an increasingly polarizing debate. Here we intend to provide an overview on recent progress in biomedical and biotechnological applications of synthetic genomics and synthetic biology as well as on arguments and evidence related to their possible benefits, risks and governance implications. PMID:23997647

Photoionization of water molecules by a train of attosecond pulses assisted by a near-infrared laser: delay and polarization control

NASA Astrophysics Data System (ADS)

Martini, Lara; Boll, Diego I. R.; Fojón, Omar A.

2017-08-01

Basic reactions involving water molecules are essential to understand the interaction between radiation and the biological tissue because living cells are composed mostly by water. Therefore, the knowledge of ionization of the latter is crucial in many domains of Biology and Physics. So, we study theoretically the photoionization of water molecules by extreme ultraviolet attopulse trains assisted by lasers in the near-infrared range. We use a separable Coulomb-Volkov model in which the temporal evolution of the system can be divided into three stages allowing spatial and temporal separation for the Coulomb and Volkov final state wavefunctions. First, we analyze photoelectron angular distributions for different delays between the attopulse train and the assistant laser field. We compare our results for water and Ne atoms as they belong to the same isoelectronic series. Moreover, we contrast our calculations with previous theoretical and experimental work for Ar atoms due to the similarities of the orbitals involved in the reaction. Second, we study the effect of varying the relative orientations of the attopulse and laser field polarizations and we compare our predictions with other theories and experiments. We expect these studies contribute to the improvement of polarization experiments and the development of the attopulse trains and assistant laser fields technologies. Finally, we hope our work promote progress on the control of the chemical reactivity of water molecules since this could be useful in different fields such as radiobiology and medical physics.

Recent Developments of Liposomes as Nanocarriers for Theranostic Applications

PubMed Central

Xing, Hang; Hwang, Kevin; Lu, Yi

2016-01-01

Liposomes are nanocarriers comprised of lipid bilayers encapsulating an aqueous core. The ability of liposomes to encapsulate a wide variety of diagnostic and therapeutic agents has led to significant interest in utilizing liposomes as nanocarriers for theranostic applications. In this review, we highlight recent progress in developing liposomes as nanocarriers for a) diagnostic applications to detect proteins, DNA, and small molecule targets using fluorescence, magnetic resonance, ultrasound, and nuclear imaging; b) therapeutic applications based on small molecule-based therapy, gene therapy and immunotherapy; and c) theranostic applications for simultaneous detection and treatment of heavy metal toxicity and cancers. In addition, we summarize recent studies towards understanding of interactions between liposomes and biological components. Finally, perspectives on future directions in advancing the field for clinical translations are also discussed. PMID:27375783

EZH2: biology, disease, and structure-based drug discovery

PubMed Central

Tan, Jin-zhi; Yan, Yan; Wang, Xiao-xi; Jiang, Yi; Xu, H Eric

2014-01-01

EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is a highly conserved histone methyltransferase that methylates lysine 27 of histone 3. Overexpression of EZH2 has been found in a wide range of cancers, including those of the prostate and breast. In this review, we address the current understanding of the oncogenic role of EZH2, including its PRC2-dependent transcriptional repression and PRC2-independent gene activation. We also discuss the connections between EZH2 and other silencing enzymes, such as DNA methyltransferase and histone deacetylase. We comprehensively address the architecture of the PRC2 complex and the crucial roles of each subunit. Finally, we summarize new progress in developing EZH2 inhibitors, which could be a new epigenetic therapy for cancers. PMID:24362326

Recent progress on magnetic iron oxide nanoparticles: synthesis, surface functional strategies and biomedical applications

PubMed Central

Wu, Wei; Wu, Zhaohui; Yu, Taekyung; Jiang, Changzhong; Kim, Woo-Sik

2015-01-01

This review focuses on the recent development and various strategies in the preparation, microstructure, and magnetic properties of bare and surface functionalized iron oxide nanoparticles (IONPs); their corresponding biological application was also discussed. In order to implement the practical in vivo or in vitro applications, the IONPs must have combined properties of high magnetic saturation, stability, biocompatibility, and interactive functions at the surface. Moreover, the surface of IONPs could be modified by organic materials or inorganic materials, such as polymers, biomolecules, silica, metals, etc. The new functionalized strategies, problems and major challenges, along with the current directions for the synthesis, surface functionalization and bioapplication of IONPs, are considered. Finally, some future trends and the prospects in these research areas are also discussed. PMID:27877761

LipidII: Just Another Brick in the Wall?

PubMed Central

Scheffers, Dirk-Jan; Tol, Menno B.

2015-01-01

Nearly all bacteria contain a peptidoglycan cell wall. The peptidoglycan precursor molecule is LipidII, containing the basic peptidoglycan building block attached to a lipid. Although the suitability of LipidII as an antibacterial target has long been recognized, progress on elucidating the role(s) of LipidII in bacterial cell biology has been slow. The focus of this review is on exciting new developments, both with respect to antibacterials targeting LipidII as well as the emerging role of LipidII in organizing the membrane and cell wall synthesis. It appears that on both sides of the membrane, LipidII plays crucial roles in organizing cytoskeletal proteins and peptidoglycan synthesis machineries. Finally, the recent discovery of no less than three different categories of LipidII flippases will be discussed. PMID:26679002

[Application of THz technology to nondestructive detection of agricultural product quality].

PubMed

Jiang, Yu-ying; Ge, Hong-yi; Lian, Fei-yu; Zhang, Yuan; Xia, Shan-hong

2014-08-01

With recent development of THz sources and detector, applications of THz radiation to nondestructive testing and quality control have expanded in many fields, such as agriculture, safety inspection and quality control, medicine, biochemistry, communication etc. Compared with other detection technique, being a new kind of technique, THz radiation has low energy, good perspectivity, and high signal-to-noise ratio, and thus can obtain physical, chemical and biological information. This paper first introduces the basic concept of THz radiation and the major properties, then gives an extensive review of recent research progress in detection of the quality of agricultural products via THz technique, analyzes the existing shortcomings of THz detection and discusses the outlook of potential application, finally proposes the new application of THz technique to detection of quality of stored grain.

The Problem of Extraterrestrial Civilizations and Extrasolar Planets

NASA Astrophysics Data System (ADS)

Mickaelian, A. M.

2015-07-01

The problem of extraterrestrial intelligence is the best example of multidisciplinary science. Here philosophy and religion, astronomy, radiophysics, spectrography, space flights and astronautics, geology and planetology, astroecology, chemistry and biology, history and archaeology, psychology, sociology, linguistics, diplomacy, UFOs and peculiar phenomena are involved. Among these many-sided studies, astronomers have probably displayed the most progress by discovering thousands of extrasolar planets. At present, a number of search programs are being accomplished, including those with space telescopes, and planets in so-called "habitable zone" are considered as most important ones, for which various orbital and physical parameters are being calculated. As the discovery of extraterrestrial life is the final goal, a special attention is given to Earth-like planets, for the discovery of which most sensitive technical means are necessary.

Recent Developments in Synthetic Carbohydrate-Based Diagnostics, Vaccines, and Therapeutics.

PubMed

Fernández-Tejada, Alberto; Cañada, F Javier; Jiménez-Barbero, Jesús

2015-07-20

Glycans are everywhere in biological systems, being involved in many cellular events with important implications for medical purposes. Building upon a detailed understanding of the functional roles of carbohydrates in molecular recognition processes and disease states, glycans are increasingly being considered as key players in pharmacological research. On the basis of the important progress recently made in glycochemistry, glycobiology, and glycomedicine, we provide a complete overview of successful applications and future perspectives of carbohydrates in the biopharmaceutical and medical fields. This review highlights the development of carbohydrate-based diagnostics, exemplified by glycan imaging techniques and microarray platforms, synthetic oligosaccharide vaccines against infectious diseases (e.g., HIV) and cancer, and finally carbohydrate-derived therapeutics, including glycomimetic drugs and glycoproteins. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modular and Orthogonal Synthesis of Hybrid Polymers and Networks

PubMed Central

Liu, Shuang; Dicker, Kevin T.; Jia, Xinqiao

2015-01-01

Biomaterials scientists strive to develop polymeric materials with distinct chemical make-up, complex molecular architectures, robust mechanical properties and defined biological functions by drawing inspirations from biological systems. Salient features of biological designs include (1) repetitive presentation of basic motifs; and (2) efficient integration of diverse building blocks. Thus, an appealing approach to biomaterials synthesis is to combine synthetic and natural building blocks in a modular fashion employing novel chemical methods. Over the past decade, orthogonal chemistries have become powerful enabling tools for the modular synthesis of advanced biomaterials. These reactions require building blocks with complementary functionalities, occur under mild conditions in the presence of biological molecules and living cells and proceed with high yield and exceptional selectivity. These chemistries have facilitated the construction of complex polymers and networks in a step-growth fashion, allowing facile modulation of materials properties by simple variations of the building blocks. In this review, we first summarize features of several types of orthogonal chemistries. We then discuss recent progress in the synthesis of step growth linear polymers, dendrimers and networks that find application in drug delivery, 3D cell culture and tissue engineering. Overall, orthogonal reactions and modulular synthesis have not only minimized the steps needed for the desired chemical transformations but also maximized the diversity and functionality of the final products. The modular nature of the design, combined with the potential synergistic effect of the hybrid system, will likely result in novel hydrogel matrices with robust structures and defined functions. PMID:25572255

Systems biology: A tool for charting the antiviral landscape.

PubMed

Bowen, James R; Ferris, Martin T; Suthar, Mehul S

2016-06-15

The host antiviral programs that are initiated following viral infection form a dynamic and complex web of responses that we have collectively termed as "the antiviral landscape". Conventional approaches to studying antiviral responses have primarily used reductionist systems to assess the function of a single or a limited subset of molecules. Systems biology is a holistic approach that considers the entire system as a whole, rather than individual components or molecules. Systems biology based approaches facilitate an unbiased and comprehensive analysis of the antiviral landscape, while allowing for the discovery of emergent properties that are missed by conventional approaches. The antiviral landscape can be viewed as a hierarchy of complexity, beginning at the whole organism level and progressing downward to isolated tissues, populations of cells, and single cells. In this review, we will discuss how systems biology has been applied to better understand the antiviral landscape at each of these layers. At the organismal level, the Collaborative Cross is an invaluable genetic resource for assessing how genetic diversity influences the antiviral response. Whole tissue and isolated bulk cell transcriptomics serves as a critical tool for the comprehensive analysis of antiviral responses at both the tissue and cellular levels of complexity. Finally, new techniques in single cell analysis are emerging tools that will revolutionize our understanding of how individual cells within a bulk infected cell population contribute to the overall antiviral landscape. Copyright © 2016 Elsevier B.V. All rights reserved.

Content and format of labeling for human prescription drug and biological products; requirements for pregnancy and lactation labeling. Final rule.

PubMed

2014-12-04

The Food and Drug Administration (FDA) is amending its regulations governing the content and format of the "Pregnancy," "Labor and delivery," and "Nursing mothers" subsections of the "Use in Specific Populations" section of the labeling for human prescription drug and biological products. The final rule requires the removal of the pregnancy categories A, B, C, D, and X from all human prescription drug and biological product labeling. For human prescription drug and biological products subject to the Agency's 2006 Physician Labeling Rule, the final rule requires that the labeling include a summary of the risks of using a drug during pregnancy and lactation, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy and lactation. The final rule eliminates the "Labor and delivery" subsection because information about labor and delivery is included in the "Pregnancy" subsection. The final rule requires that the labeling include relevant information about pregnancy testing, contraception, and infertility for health care providers prescribing for females and males of reproductive potential. The final rule creates a consistent format for providing information about the risks and benefits of prescription drug and/or biological product use during pregnancy and lactation and by females and males of reproductive potential. These revisions will facilitate prescriber counseling for these populations.

[Ethical viewpoints on cryopreservation of human embryos].

PubMed

Weiler, R

1991-01-01

In the introduction the author describes how moral judgements are being formed in the pluralistic structures of today's societies. Moral relativism and subjectivism are the wide spread consequences of empirical anthropological theories. In this situation the necessity of an objective and normative moral theory (Christian natural law theory) is being stressed. Neither biology nor medicine can pronounce final judgements on the value of human life. The arguments in favour of cryoconservation (medical progress, parents wish to have children, cost-reduction) are outweighed by those arguments which maintain that man cannot dispose of human life through the manipulation of the progenitive act outside marriage and of the juman act of procreation. There are also the risks and the endangering of the human value of the embryo, up to prolicide which is considered to be permissible in some cases, on these moral grounds the author objects to the cryoconservation of embryos as does the relevant instruction of the papal magisterium of the Roman Catholic Church (Donum vitae 1987). He does not, however, take a final stance on how the subjective decision of the physician is to be judged in the individual case.

Metabolic support for a lunar base

NASA Technical Reports Server (NTRS)

Sauer, R. L.

1985-01-01

A review of the metabolic support systems used and the metabolic support requirements provided on past and current spaceflight programs is presented. This review will provide familiarization with unique constraints of space flight and technology as it relates to inflight metabolic support of astronauts. This information, along with a general review of the NASA effort to develop a Controlled Ecological Life Support System (CELSS) will define the general scenario of metabolic support for a lunar base. A phased program of metabolic support for a lunar base will be elucidated. Included will be discussion of the CELSS water reclamation and food recycling technology as it now exists and how it could be expected to be progressively incorporated into the lunar base. This transition would be from a relatively open system in the initial development period, when mechanical phase change water reclamation and minimal plant growth are incorporated, to the final period when practically total closure of the life support system will be proved through physicochemical and biological processes. Finally, a review of the estimated metabolic intake requirements for the occupants of a lunar base will be presented.

Guaranteed Time Observations Support for Goddard High Resolution Spectrograph (GHRS) on HST

NASA Technical Reports Server (NTRS)

Beaver, Edward

1998-01-01

We assemble this final grant report by combining our previously submitted progress reports with the last year's progress report. Section 2 is the progress report for the June 1, 1991 to Nov. 14, 1995 period. Section 4 is the progress report for the Nov. 14, 1996 to Dec. 31, 1996 period. Section 5 is the progress report for the Nov. 14 to Aug. 31, 1997 period. Section 6 is the new progress report for the Sept. 15, 1997 to Nov. 14, 1998 final period. Section 3 is a summary of our spare detector high voltage transient tests activity in 1992 in support of the renewed safe operation of the GHRS HST D1 detector. Note that we have left the format of each progress report the same as originally sent out. The slight differences in format presentation are thus intended.

Biomedically relevant circuit-design strategies in mammalian synthetic biology

PubMed Central

Bacchus, William; Aubel, Dominique; Fussenegger, Martin

2013-01-01

The development and progress in synthetic biology has been remarkable. Although still in its infancy, synthetic biology has achieved much during the past decade. Improvements in genetic circuit design have increased the potential for clinical applicability of synthetic biology research. What began as simple transcriptional gene switches has rapidly developed into a variety of complex regulatory circuits based on the transcriptional, translational and post-translational regulation. Instead of compounds with potential pharmacologic side effects, the inducer molecules now used are metabolites of the human body and even members of native cell signaling pathways. In this review, we address recent progress in mammalian synthetic biology circuit design and focus on how novel designs push synthetic biology toward clinical implementation. Groundbreaking research on the implementation of optogenetics and intercellular communications is addressed, as particularly optogenetics provides unprecedented opportunities for clinical application. Along with an increase in synthetic network complexity, multicellular systems are now being used to provide a platform for next-generation circuit design. PMID:24061539

Conceptual Barriers to Progress Within Evolutionary Biology

PubMed Central

Laland, Kevin N.; Odling-Smee, John; Feldman, Marcus W.; Kendal, Jeremy

2011-01-01

In spite of its success, Neo-Darwinism is faced with major conceptual barriers to further progress, deriving directly from its metaphysical foundations. Most importantly, neo-Darwinism fails to recognize a fundamental cause of evolutionary change, “niche construction”. This failure restricts the generality of evolutionary theory, and introduces inaccuracies. It also hinders the integration of evolutionary biology with neighbouring disciplines, including ecosystem ecology, developmental biology, and the human sciences. Ecology is forced to become a divided discipline, developmental biology is stubbornly difficult to reconcile with evolutionary theory, and the majority of biologists and social scientists are still unhappy with evolutionary accounts of human behaviour. The incorporation of niche construction as both a cause and a product of evolution removes these disciplinary boundaries while greatly generalizing the explanatory power of evolutionary theory. PMID:21572912

Conceptual Barriers to Progress Within Evolutionary Biology.

PubMed

Laland, Kevin N; Odling-Smee, John; Feldman, Marcus W; Kendal, Jeremy

2009-08-01

In spite of its success, Neo-Darwinism is faced with major conceptual barriers to further progress, deriving directly from its metaphysical foundations. Most importantly, neo-Darwinism fails to recognize a fundamental cause of evolutionary change, "niche construction". This failure restricts the generality of evolutionary theory, and introduces inaccuracies. It also hinders the integration of evolutionary biology with neighbouring disciplines, including ecosystem ecology, developmental biology, and the human sciences. Ecology is forced to become a divided discipline, developmental biology is stubbornly difficult to reconcile with evolutionary theory, and the majority of biologists and social scientists are still unhappy with evolutionary accounts of human behaviour. The incorporation of niche construction as both a cause and a product of evolution removes these disciplinary boundaries while greatly generalizing the explanatory power of evolutionary theory.

21 CFR 601.70 - Annual progress reports of postmarketing studies.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Annual progress reports of postmarketing studies... SERVICES (CONTINUED) BIOLOGICS LICENSING Postmarketing Studies § 601.70 Annual progress reports of postmarketing studies. (a) General requirements. This section applies to all required postmarketing studies (e.g...

21 CFR 601.70 - Annual progress reports of postmarketing studies.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Annual progress reports of postmarketing studies... SERVICES (CONTINUED) BIOLOGICS LICENSING Postmarketing Studies § 601.70 Annual progress reports of postmarketing studies. (a) General requirements. This section applies to all required postmarketing studies (e.g...

Unique case of oligoastrocytoma with recurrence and grade progression: Exhibiting differential expression of high mobility group-A1 and human telomerase reverse transcriptase

PubMed Central

Gandhi, Puneet; Khare, Richa; Niraj, Kavita; Garg, Nitin; Sorte, Sandeep K; Gulwani, Hanni

2016-01-01

Mixed gliomas, primarily oligoastrocytomas, account for about 5%-10% of all gliomas. Distinguishing oligoastrocytoma based on histological features alone has limitations in predicting the exact biological behavior, necessitating ancillary markers for greater specificity. In this case report, human telomerase reverse transcriptase (hTERT) and high mobility group-A1 (HMGA1); markers of proliferation and stemness, have been quantitatively analyzed in formalin-fixed paraffin-embedded tissue samples of a 34 years old patient with oligoastrocytoma. Customized florescence-based immunohistochemistry protocol with enhanced sensitivity and specificity is used in the study. The patient presented with a history of generalized seizures and his magnetic resonance imaging scans revealed infiltrative ill-defined mass lesion with calcified foci within the left frontal white matter, suggestive of glioma. He was surgically treated at our center for four consecutive clinical events. Histopathologically, the tumor was identified as oligoastrocytoma-grade II followed by two recurrence events and final progression to grade III. Overall survival of the patient without adjuvant therapy was more than 9 years. Glial fibrillary acidic protein, p53, Ki-67, nuclear atypia index, pre-operative neutrophil-lymphocyte ratio, are the other parameters assessed. Findings suggest that hTERT and HMGA1 are linked to tumor recurrence and progression. Established markers can assist in defining precise histopathological grade in conjuction with conventional markers in clinical setup. PMID:27672647

Progressive Stochastic Reconstruction Technique (PSRT) for cryo electron tomography.

PubMed

Turoňová, Beata; Marsalek, Lukas; Davidovič, Tomáš; Slusallek, Philipp

2015-03-01

Cryo Electron Tomography (cryoET) plays an essential role in Structural Biology, as it is the only technique that allows to study the structure of large macromolecular complexes in their close to native environment in situ. The reconstruction methods currently in use, such as Weighted Back Projection (WBP) or Simultaneous Iterative Reconstruction Technique (SIRT), deliver noisy and low-contrast reconstructions, which complicates the application of high-resolution protocols, such as Subtomogram Averaging (SA). We propose a Progressive Stochastic Reconstruction Technique (PSRT) - a novel iterative approach to tomographic reconstruction in cryoET based on Monte Carlo random walks guided by Metropolis-Hastings sampling strategy. We design a progressive reconstruction scheme to suit the conditions present in cryoET and apply it successfully to reconstructions of macromolecular complexes from both synthetic and experimental datasets. We show how to integrate PSRT into SA, where it provides an elegant solution to the region-of-interest problem and delivers high-contrast reconstructions that significantly improve template-based localization without any loss of high-resolution structural information. Furthermore, the locality of SA is exploited to design an importance sampling scheme which significantly speeds up the otherwise slow Monte Carlo approach. Finally, we design a new memory efficient solution for the specimen-level interior problem of cryoET, removing all associated artifacts. Copyright © 2015 Elsevier Inc. All rights reserved.

AB72. Mysteries of TGF-β paradox in benign and malignant cells

PubMed Central

Lee, Chung; Grayhack, John T.

2014-01-01

TGF-β regulates a wide range of biological functions including embryonic development, wound healing, organogenesis, immune modulation, and cancer progression. Interestingly, TGF-β is known to inhibit cell growth in benign cells but promote progression in cancer cells, a phenomenon known as TGF-β paradox. To date, the mechanism of this paradox still remains as a scientific mystery. In this review, we present our experience, alone with the literature, in an attempt to offer answers to this mystery. First, we observed that, upon TGF-β engagement, there is a differential activation of Erk between benign and cancer cells. Since activated Erk is a major mediator in tumor progression and metastasis, a differentially activated Erk represents the answer to this mystery. Second, we identified a key player, PP2A-B56α, which is differentially recruited by the activated type I TGF-β receptor (TBRI) in benign and tumor cells, resulting in differential Erk activation. Finally, TGF-β stimulation leads to a suppressed TBRs in tumor cells but not in benign cells. This differentially suppressed TBRs triggers differential recruitment of PP2A-B56α and, thus, differential activation of Erk. The above three events offer the explanation to the mysteries of TGF-β paradox. Understanding the mechanism of TGF-β paradox will help us to predict indolent from aggressive cancers and will help us to develop novel anti-cancer strategies.

Mysteries of TGF-β Paradox in Benign and Malignant Cells.

PubMed

Zhang, Qiang; Yu, Nengwang; Lee, Chung

2014-01-01

TGF-β regulates a wide range of biological functions including embryonic development, wound healing, organogenesis, immune modulation, and cancer progression. Interestingly, TGF-β is known to inhibit cell growth in benign cells but promote progression in cancer cells; this phenomenon is known as TGF-β paradox. To date, the mechanism of this paradox still remains a scientific mystery. In this review, we present our experience, along with the literature, in an attempt to answer this mystery. First, we observed that, on TGF-β engagement, there is a differential activation of Erk between benign and cancer cells. Since activated Erk is a major mediator in tumor progression and metastasis, a differentially activated Erk represents the answer to this mystery. Second, we identified a key player, PP2A-B56α, which is differentially recruited by the activated type I TGF-β receptor (TBRI) in benign and tumor cells, resulting in differential Erk activation. Finally, TGF-β stimulation leads to suppressed TBRs in tumor cells but not in benign cells. This differentially suppressed TBRs triggers differential recruitment of PP2A-B56α and, thus, differential activation of Erk. The above three events explain the mysteries of TGF-β paradox. Understanding the mechanism of TGF-β paradox will help us to predict indolent from aggressive cancers and develop novel anti-cancer strategies.

Mysteries of TGF-β Paradox in Benign and Malignant Cells

PubMed Central

Zhang, Qiang; Yu, Nengwang; Lee, Chung

2014-01-01

TGF-β regulates a wide range of biological functions including embryonic development, wound healing, organogenesis, immune modulation, and cancer progression. Interestingly, TGF-β is known to inhibit cell growth in benign cells but promote progression in cancer cells; this phenomenon is known as TGF-β paradox. To date, the mechanism of this paradox still remains a scientific mystery. In this review, we present our experience, along with the literature, in an attempt to answer this mystery. First, we observed that, on TGF-β engagement, there is a differential activation of Erk between benign and cancer cells. Since activated Erk is a major mediator in tumor progression and metastasis, a differentially activated Erk represents the answer to this mystery. Second, we identified a key player, PP2A-B56α, which is differentially recruited by the activated type I TGF-β receptor (TBRI) in benign and tumor cells, resulting in differential Erk activation. Finally, TGF-β stimulation leads to suppressed TBRs in tumor cells but not in benign cells. This differentially suppressed TBRs triggers differential recruitment of PP2A-B56α and, thus, differential activation of Erk. The above three events explain the mysteries of TGF-β paradox. Understanding the mechanism of TGF-β paradox will help us to predict indolent from aggressive cancers and develop novel anti-cancer strategies. PMID:24860782

A brief history of the Japan Society for Cell Biology.

PubMed

Tashiro, Y; Okigaki, T

2001-02-01

The Japan Society for Cell Biology (JSCB) was first founded in 1950 as the Japan Society for Cellular Chemistry under the vigorous leadership of Seizo Katsunuma, in collaboration with Shigeyasu Amano and Satimaru Seno. The Society was provisionally named as above simply because cell biology had not yet been coined at that time in Japan, although in prospect and reality the Society was in fact for the purpose of pursuing cell biology. Later in 1964, the Society was properly renamed as the Japan Society for Cell Biology. After this renaming, the JSCB made great efforts to adapt itself to the rapid progress being made in cell biology. For this purpose the Society's constitution was created in 1966 and revised in 1969. According to the revised constitution, the President, Executive Committee and Councils were to be determined by ballot vote. The style of the annual meetings was gradually modified to incorporate general oral and poster presentations in addition to Symposia (1969-1974). The publication of annual periodicals in Japanese called Symposia of the Japan Society for Cellular Chemistry (1951-1967) and later Symposia of the Japan Society for Cell Biology (1968-1974) was replaced by a new international journal called Cell Structure and Function initiated in 1975. This reformation made it possible for the Society to participate in the Science Council of Japan in 1975 and finally in 1993 to acquire its own study section of Cell Biology with grants-in-aid from the Ministry of Education and Science, Japan. The JSCB hosted the 3rd International Congress on Cell Biology (ICCB) in 1984 and the 3rd Asian-Pacific Organization for Cell Biology (APOCB) Congress in 1998, thus contributing to the international advancement of cell biology. Now the membership of JSCB stands at approximately 1,800 and the number of presentations per meeting is 300 to 400 annually. Although a good number of interesting and important findings in cell biology have been reported from Japan, the general academic activity of the JSCB is far less than one might expect. This is simply due the fact that academic activity in the field of cell biology in Japan is divided among several other related societies such as the Japan Society for Molecular Biology and the Japan Society for Developmental Biology, among others.

Reciprocity within biochemistry and biology service-learning.

PubMed

Santas, Amy J

2009-05-01

Service-learning has become a popular pedagogy because of its numerous and far-reaching benefits (e.g. student interest, engagement, and retention). In part, the benefits are a result of the student learning while providing a service that reflects a true need-not simply an exercise. Although service-learning projects have been developed in the areas of Biochemistry and Biology, many do not require reciprocity between the student and those being served. A reciprocal relationship enables a depth in learning as students synthesize and integrate their knowledge while confronting a real-life need. A novel reciprocal service-learning project within a three-semester undergraduate research course in the areas of Biochemistry and Biology is presented. The goal of the project was agreed upon through joint meetings with the partner institution (The Wilds) to develop an in-house competitive ELISA pregnane diol assay. Student progress and achievements were followed through the use of rubrics and progress-meetings with The Wilds. A portfolio provided a visual of progress as it contained both the written assignments as well as the rubric. The article describes a specific reciprocal biochemistry and biology service-learning project and provides recommendations on how to adapt this service-learning design for use in other research courses. Copyright © 2009 International Union of Biochemistry and Molecular Biology, Inc.

Regulatory Oversight of Cell and Gene Therapy Products in Canada.

PubMed

Ridgway, Anthony; Agbanyo, Francisca; Wang, Jian; Rosu-Myles, Michael

2015-01-01

Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTPs) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTPs, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonisation at an international level are essential for progress in the development and commercialisation of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking.

A Comparison of Nurses’ Activities Under Two Models of Administration

DTIC Science & Technology

1985-08-01

Angela Sheehan, "Innovation in Cancer Nursing and the Role of the Nurse in Clinical Trials," Progress in Clinical and Biological Research 121 (1983): 87...by Diagnosis-Related Groups,* Annals of Internal Medicine 100 (April 1984): 576. 12Tony DeCrosta, " Megatrends in Nursing: 10 New Directions that are...in Clinical Trials." Progress in Clinical and Biological Research 121 (1983): 87-92. Beyers, Marjorie: Byre, Calvin: Levy, Paul: Mallin, Katherine

Biology of Metastatic Renal Cell Carcinoma

PubMed Central

Milella, Michele; Felici, Alessandra

2011-01-01

In the past ten years we have made exceptional progresses in the understanding of RCC biology, particularly by recognizing the crucial pathogenetic role of activation of the HIF/VEGF and mTOR pathways. This has resulted in the successful clinical development of anti-angiogenic and mTOR-targeted drugs, which have profoundly impacted on the natural history of the disease and have improved the duration and quality of RCC patient lives. However, further improvements are still greatly needed: 1) even in patients who obtain striking clinical responses early in the course of treatment, disease will ultimately escape control and progress to a treatment-resistant state, leading to therapeutic failure; 2) prolonged disease control usually requires 'continuous' treatment, even across different treatment lines, making the impact of chronic, low-grade, toxicities on quality of life greater and precluding, for most patients, the possibility of experiencing 'drug-free holidays'; 3) although we have successfully identified classes of drugs (or molecular mechanisms of action) that are effective in a substantial proportion of patients, we still fall short of molecular predictive factors that identify individual patients who will (or will not) benefit from a specific intervention and still proceed on a trial-and-error basis, far from a truly 'personalized' therapeutic approach; 4) finally (and perhaps most importantly), even in the best case scenario, currently available treatments inevitably fail to definitively 'cure' metastatic RCC patients. In this review we briefly summarize recent developments in the understanding of the molecular pathogenesis of RCC, the development of resistance/escape mechanisms, the rationale for sequencing agents with different mechanisms of action, and the importance of host-related factors. Unraveling the complex mechanisms by which RCC shapes host microenvironment and immune response and therapeutic treatments, in turn, shape both cancer cell biology and tumor-host interactions may hold the key to future advances in such a complex and challenging disease. PMID:21850209

Biology of metastatic renal cell carcinoma.

PubMed

Milella, Michele; Felici, Alessandra

2011-01-01

In the past ten years we have made exceptional progresses in the understanding of RCC biology, particularly by recognizing the crucial pathogenetic role of activation of the HIF/VEGF and mTOR pathways. This has resulted in the successful clinical development of anti-angiogenic and mTOR-targeted drugs, which have profoundly impacted on the natural history of the disease and have improved the duration and quality of RCC patient lives. However, further improvements are still greatly needed: 1) even in patients who obtain striking clinical responses early in the course of treatment, disease will ultimately escape control and progress to a treatment-resistant state, leading to therapeutic failure; 2) prolonged disease control usually requires 'continuous' treatment, even across different treatment lines, making the impact of chronic, low-grade, toxicities on quality of life greater and precluding, for most patients, the possibility of experiencing 'drug-free holidays'; 3) although we have successfully identified classes of drugs (or molecular mechanisms of action) that are effective in a substantial proportion of patients, we still fall short of molecular predictive factors that identify individual patients who will (or will not) benefit from a specific intervention and still proceed on a trial-and-error basis, far from a truly 'personalized' therapeutic approach; 4) finally (and perhaps most importantly), even in the best case scenario, currently available treatments inevitably fail to definitively 'cure' metastatic RCC patients. In this review we briefly summarize recent developments in the understanding of the molecular pathogenesis of RCC, the development of resistance/escape mechanisms, the rationale for sequencing agents with different mechanisms of action, and the importance of host-related factors. Unraveling the complex mechanisms by which RCC shapes host microenvironment and immune response and therapeutic treatments, in turn, shape both cancer cell biology and tumor-host interactions may hold the key to future advances in such a complex and challenging disease.

I love you with all my brain: laying aside the intellectually dull sword of biological determinism

PubMed Central

Woodson, James C.

2012-01-01

Background By organizing and activating our passions with both hormones and experiences, the heart and mind of sexual behavior, sexual motivation, and sexual preference is the brain, the organ of learning. Despite decades of progress, this incontrovertible truth is somehow lost in the far-too-often biologically deterministic interpretation of genetic, hormonal, and anatomical scientific research into the biological origins of sexual motivation. Simplistic and polarized arguments are used in the media by both sides of the seemingly endless debate over sexual orientation, equality, and human rights with such catch phrases as ‘born gay’ contrasted against attempts of “reparative therapy” or “pray the gay away”. Though long abandoned in practically every other area of psychology, this remnant of the nature-nurture controversy remains despite its generally acknowledged insufficiency in explaining any adult aspect of the human condition within the scientific community. Methods This theoretical review article identifies three factors: 1) good intentions with regard to the argument from immutability; 2) false dichotomies limiting intellectual progress by oversimplification of theory and thus hypothesis, and most dangerously, interpretation and; 3) Tradition: a historical separation of the disciplines of biology and psychology, which, to this day, interferes with the effective translation of well-conducted science into good public understanding and policy. Results Studies clearly demonstrate that progress toward sexual-orientation equality is being made, if slowly, despite the apparent irrelevance of the “born gay” argument from immutability. Evidence is further provided supporting the inadequacy of polarized, dichotic theories of sexual development, particularly those pitting “blank slate learning” against a fated, deterministic biological perspective. Results of this review suggest that an emerging interactionist perspective will promote both better scientific progress and better public understanding, hopefully contributing to progress toward nondiscriminatory public policy. Conclusion Accepting that the brain is a highly plastic, modularly dimorphic, developmentally biased organ of learning, one which is organized and activated by both hormones and experiences across the lifespan, is essential for doing “good science” well. Interactionist theories of psychosexual development provide an empirically sound, strong, yet modifiable foundation for testable hypotheses exploring biologically biased sexual learning. PMID:24693345

I love you with all my brain: laying aside the intellectually dull sword of biological determinism.

PubMed

Woodson, James C

2012-01-01

By organizing and activating our passions with both hormones and experiences, the heart and mind of sexual behavior, sexual motivation, and sexual preference is the brain, the organ of learning. Despite decades of progress, this incontrovertible truth is somehow lost in the far-too-often biologically deterministic interpretation of genetic, hormonal, and anatomical scientific research into the biological origins of sexual motivation. Simplistic and polarized arguments are used in the media by both sides of the seemingly endless debate over sexual orientation, equality, and human rights with such catch phrases as 'born gay' contrasted against attempts of "reparative therapy" or "pray the gay away". Though long abandoned in practically every other area of psychology, this remnant of the nature-nurture controversy remains despite its generally acknowledged insufficiency in explaining any adult aspect of the human condition within the scientific community. THIS THEORETICAL REVIEW ARTICLE IDENTIFIES THREE FACTORS: 1) good intentions with regard to the argument from immutability; 2) false dichotomies limiting intellectual progress by oversimplification of theory and thus hypothesis, and most dangerously, interpretation and; 3) Tradition: a historical separation of the disciplines of biology and psychology, which, to this day, interferes with the effective translation of well-conducted science into good public understanding and policy. Studies clearly demonstrate that progress toward sexual-orientation equality is being made, if slowly, despite the apparent irrelevance of the "born gay" argument from immutability. Evidence is further provided supporting the inadequacy of polarized, dichotic theories of sexual development, particularly those pitting "blank slate learning" against a fated, deterministic biological perspective. Results of this review suggest that an emerging interactionist perspective will promote both better scientific progress and better public understanding, hopefully contributing to progress toward nondiscriminatory public policy. Accepting that the brain is a highly plastic, modularly dimorphic, developmentally biased organ of learning, one which is organized and activated by both hormones and experiences across the lifespan, is essential for doing "good science" well. Interactionist theories of psychosexual development provide an empirically sound, strong, yet modifiable foundation for testable hypotheses exploring biologically biased sexual learning.

The BIOSCI electronic newsgroup network for the biological sciences. Final report, October 1, 1992--June 30, 1996

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

Kristofferson, D.; Mack, D.

1996-10-01

This is the final report for a DOE funded project on BIOSCI Electronic Newsgroup Network for the biological sciences. A usable network for scientific discussion, major announcements, problem solving, etc. has been created.

Antibodies to the HIV-1 Tat protein correlated with nonprogression to AIDS: a rationale for the use of Tat toxoid as an HIV-1 vaccine.

PubMed

Zagury, J F; Sill, A; Blattner, W; Lachgar, A; Le Buanec, H; Richardson, M; Rappaport, J; Hendel, H; Bizzini, B; Gringeri, A; Carcagno, M; Criscuolo, M; Burny, A; Gallo, R C; Zagury, D

1998-01-01

To investigate which immune parameters, such as antibodies against HIV-1 specificities, or viral parameters, such as p24 antigenemia, are predictive of disease progression. We performed studies on serum collected from individuals exhibiting two extremes of disease evolution--67 fast progressors (FP) and 182 nonprogressors (NP)--at their enrollment. After a 1- to 2-year clinical follow-up of 104 nonprogressors after their enrollment, we could determine the best serologic predictors for disease progression. We investigated levels of antibodies to tetanus toxoid and to HIV antigens including Env, Gag, Nef, and Tat proteins, as well as p24 antigenemia, viremia, CD4 cell count, and interferon-alpha (IFN-alpha) titers in FPs and NPs, and we correlated these data with clinical and biologic signs of progression. p24 Antigenemia, a marker of viral replication, and anti-Tat antibodies were highly and inversely correlated in both groups (P < .001). Furthermore, anti-p24 antibodies and low serum IFN-alpha levels were correlated to the NP versus the FP cohort. Finally, among NPs, only antibodies to Tat and not to the other HIV specificities (Env, Nef, Gag) were significantly predictive of clinical stability during their follow-up. Antibodies toward HIV-1 Tat, which are inversely correlated to p24 antigenemia, appear as a critical marker for a lack of disease progression. This study strongly suggests that rising anti-Tat antibodies through active immunization may be beneficial in AIDS vaccine development to control viral replication.

Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression.

PubMed

Tso, For Yue; Abrahamyan, Levon; Hu, Shiu-Lok; Ruprecht, Ruth M; Wood, Charles

2013-01-01

A better understanding of how the biological functions of the HIV-1 envelope (Env) changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.

2012 Review on the Extension of the AMedP-8(C) Methodology to New Agents, Materials, and Conditions

DTIC Science & Technology

2013-10-01

Atlantic Treaty Organization (NATO) to estimate casualties from chemical, biological , radiological, and nuclear (CBRN) weapons . The final draft...chemical, biological , radiological, and nuclear (CBRN) weapons . The final draft documenting this methodology was published by IDA in 2009 and was...from Battlefield Exposure to Chemical, Biological and Radiological Agents and Nuclear Weapon Effects. IDA Document D- 4465. Alexandria, VA: IDA

Biological Sciences Curriculum Study Newsletter Number 39, BSCS Biology: A World View.

ERIC Educational Resources Information Center

Clark, George M.

Included are progress reports from forty-two countries, ranging from accounts of complete adaptation and implementation of Biological Sciences Curriculum Study (BSCS) materials to notes of preliminary contact with BSCS programs. Countries represented are: Afganistan, Argentina, Australia, Bolivia, Brazil, Canada, Central America, Ceylon, Chile,…

Overview of saltcedar biological control

Treesearch

C. Jack DeLoach; Lindsey R. Milbrath; Ray Carruthers; Allen E. Knutson; Fred Nibling; Debra Eberts; David C. Thompson; David J. Kazmer; Tom L. Dudley; Dan W. Bean; Jeff B. Knight

2006-01-01

Biological control has successfully controlled 10 exotic, invasive weeds of rangelands and natural ecosystems in the United States since 1945, and control of others is in progress. We initiated biological control of saltcedar (Tamarix spp.) in 1987, using host-specific insect herbivores that regulate saltcedar populations in the Old World. We did a...

Tumor Biology and Microenvironment Research

Cancer.gov

Part of NCI's Division of Cancer Biology's research portfolio, research in this area seeks to understand the role of tumor cells and the tumor microenvironment (TME) in driving cancer initiation, progression, maintenance and recurrence.

How Does Student Understanding of a Concept Change Throughout a Unit of Instruction? Support Toward the Theory of Learning Progressions

NASA Astrophysics Data System (ADS)

Dyer, Brian Jay

This study documented the changes in understanding a class of eighth grade high school-level biology students experienced through a biology unit introducing genetics. Learning profiles for 55 students were created using concept maps and interviews as qualitative and quantitative instruments. The study provides additional support to the theory of learning progressions called for by experts in the field. The students' learning profiles were assessed to determine the alignment with a researcher-developed learning profile. The researcher-developed learning profile incorporated the learning progressions published in the Next Generation Science Standards, as well as current research in learning progressions for 5-10th grade students studying genetics. Students were found to obtain understanding of the content in a manner that was nonlinear, even circuitous. This opposes the prevailing interpretation of learning progressions, that knowledge is ascertained in escalating levels of complexity. Learning progressions have implications in teaching sequence, assessment, education research, and policy. Tracking student understanding of other populations of students would augment the body of research and enhance generalizability.

Determination of the Biologically Relevant Sampling Depth for Terrestrial and Aquatic Ecological Risk Assessments (Final Report)

EPA Science Inventory

The Ecological Risk Assessment Support Center (ERASC) announced the release of the final report, Determination of the Biologically Relevant Sampling Depth for Terrestrial and Aquatic Ecological Risk Assessments. This technical paper provides defensible approximations fo...

Finding off-targets, biological pathways, and target diseases for chymase inhibitors via structure-based systems biology approach.

PubMed

Arooj, Mahreen; Sakkiah, Sugunadevi; Cao, Guang Ping; Kim, Songmi; Arulalapperumal, Venkatesh; Lee, Keun Woo

2015-07-01

Off-target binding connotes the binding of a small molecule of therapeutic significance to a protein target in addition to the primary target for which it was proposed. Progressively such off-targeting is emerging to be regular practice to reveal side effects. Chymase is an enzyme of hydrolase class that catalyzes hydrolysis of peptide bonds. A link between heart failure and chymase is ascribed, and a chymase inhibitor is in clinical phase II for treatment of heart failure. However, the underlying mechanisms of the off-target effects of human chymase inhibitors are still unclear. Here, we develop a robust computational strategy that is applicable to any enzyme system and that allows the prediction of drug effects on biological processes. Putative off-targets for chymase inhibitors were identified through various structural and functional similarity analyses along with molecular docking studies. Finally, literature survey was performed to incorporate these off-targets into biological pathways and to establish links between pathways and particular adverse effects. Off-targets of chymase inhibitors are linked to various biological pathways such as classical and lectin pathways of complement system, intrinsic and extrinsic pathways of coagulation cascade, and fibrinolytic system. Tissue kallikreins, granzyme M, neutrophil elastase, and mesotrypsin are also identified as off-targets. These off-targets and their associated pathways are elucidated for the effects of inflammation, cancer, hemorrhage, thrombosis, and central nervous system diseases (Alzheimer's disease). Prospectively, our approach is helpful not only to better understand the mechanisms of chymase inhibitors but also for drug repurposing exercises to find novel uses for these inhibitors. © 2014 Wiley Periodicals, Inc.

Uncovering the Mechanisms Linking Obesity and Cancer Risk

Cancer.gov

What biological processes mediate the relationship between excess body fat and increased cancer risk? Researchers are examining how hormones, inflammation, signaling molecules, and other biological factors may play a role in cancer progression.

Chemical and biological nonproliferation program. FY99 annual report

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

NONE

2000-03-01

This document is the first of what will become an annual report documenting the progress made by the Chemical and Biological Nonproliferation Program (CBNP). It is intended to be a summary of the program's activities that will be of interest to both policy and technical audiences. This report and the annual CBNP Summer Review Meeting are important vehicles for communication with the broader chemical and biological defense and nonproliferation communities. The Chemical and Biological Nonproliferation Program Strategic Plan is also available and provides additional detail on the program's context and goals. The body of the report consists of an overviewmore » of the program's philosophy, goals and recent progress in the major program areas. In addition, an appendix is provided with more detailed project summaries that will be of interest to the technical community.« less

Nuclear molecular imaging with nanoparticles: radiochemistry, applications and translation.

PubMed

Abou, D S; Pickett, J E; Thorek, D L J

2015-10-01

Molecular imaging provides considerable insight into biological processes for greater understanding of health and disease. Numerous advances in medical physics, chemistry and biology have driven the growth of this field in the past two decades. With exquisite sensitivity, depth of detection and potential for theranostics, radioactive imaging approaches have played a major role in the emergence of molecular imaging. At the same time, developments in materials science, characterization and synthesis have led to explosive progress in the nanoparticle (NP) sciences. NPs are generally defined as particles with a diameter in the nanometre size range. Unique physical, chemical and biological properties arise at this scale, stimulating interest for applications as diverse as energy production and storage, chemical catalysis and electronics. In biomedicine, NPs have generated perhaps the greatest attention. These materials directly interface with life at the subcellular scale of nucleic acids, membranes and proteins. In this review, we will detail the advances made in combining radioactive imaging and NPs. First, we provide an overview of the NP platforms and their properties. This is followed by a look at methods for radiolabelling NPs with gamma-emitting radionuclides for use in single photon emission CT and planar scintigraphy. Next, utilization of positron-emitting radionuclides for positron emission tomography is considered. Finally, recent advances for multimodal nuclear imaging with NPs and efforts for clinical translation and ongoing trials are discussed.

Nuclear molecular imaging with nanoparticles: radiochemistry, applications and translation

PubMed Central

Abou, D S; Pickett, J E

2015-01-01

Molecular imaging provides considerable insight into biological processes for greater understanding of health and disease. Numerous advances in medical physics, chemistry and biology have driven the growth of this field in the past two decades. With exquisite sensitivity, depth of detection and potential for theranostics, radioactive imaging approaches have played a major role in the emergence of molecular imaging. At the same time, developments in materials science, characterization and synthesis have led to explosive progress in the nanoparticle (NP) sciences. NPs are generally defined as particles with a diameter in the nanometre size range. Unique physical, chemical and biological properties arise at this scale, stimulating interest for applications as diverse as energy production and storage, chemical catalysis and electronics. In biomedicine, NPs have generated perhaps the greatest attention. These materials directly interface with life at the subcellular scale of nucleic acids, membranes and proteins. In this review, we will detail the advances made in combining radioactive imaging and NPs. First, we provide an overview of the NP platforms and their properties. This is followed by a look at methods for radiolabelling NPs with gamma-emitting radionuclides for use in single photon emission CT and planar scintigraphy. Next, utilization of positron-emitting radionuclides for positron emission tomography is considered. Finally, recent advances for multimodal nuclear imaging with NPs and efforts for clinical translation and ongoing trials are discussed. PMID:26133075

Biologically-inspired approaches for self-organization, adaptation, and collaboration of heterogeneous autonomous systems

NASA Astrophysics Data System (ADS)

Steinberg, Marc

2011-06-01

This paper presents a selective survey of theoretical and experimental progress in the development of biologicallyinspired approaches for complex surveillance and reconnaissance problems with multiple, heterogeneous autonomous systems. The focus is on approaches that may address ISR problems that can quickly become mathematically intractable or otherwise impractical to implement using traditional optimization techniques as the size and complexity of the problem is increased. These problems require dealing with complex spatiotemporal objectives and constraints at a variety of levels from motion planning to task allocation. There is also a need to ensure solutions are reliable and robust to uncertainty and communications limitations. First, the paper will provide a short introduction to the current state of relevant biological research as relates to collective animal behavior. Second, the paper will describe research on largely decentralized, reactive, or swarm approaches that have been inspired by biological phenomena such as schools of fish, flocks of birds, ant colonies, and insect swarms. Next, the paper will discuss approaches towards more complex organizational and cooperative mechanisms in team and coalition behaviors in order to provide mission coverage of large, complex areas. Relevant team behavior may be derived from recent advances in understanding of the social and cooperative behaviors used for collaboration by tens of animals with higher-level cognitive abilities such as mammals and birds. Finally, the paper will briefly discuss challenges involved in user interaction with these types of systems.

Palatal Seam Disintegration: To Die or Not to Die? That Is No Longer the Question

PubMed Central

Nawshad, Ali

2008-01-01

Formation of the medial epithelial seam (MES) by palatal shelf fusion is a crucial step of palate development. Complete disintegration of the MES is the final essential phase of palatal confluency with surrounding mesenchymal cells. In general, the mechanisms of palatal seam disintegration are not overwhelmingly complex, but given the large number of interacting constituents; their complicated circuitry involving feedforward, feedback, and crosstalk; and the fact that the kinetics of interaction matter, this otherwise simple mechanism can be quite difficult to interpret. As a result of this complexity, apparently simple but highly important questions remain unanswered. One such question pertains to the fate of the palatal seam. Such questions may be answered by detailed and extensive quantitative experimentation of basic biological studies (cellular, structural) and the newest molecular biological determinants (genetic/dye cell lineage, gene activity, kinase/enzyme activity), as well as animal model (knockouts, transgenic) approaches. System biology and cellular kinetics play a crucial role in cellular MES function; omissions of such critical contributors may lead to inaccurate understanding of the fate of MES. Excellent progress has been made relevant to elucidation of the mechanism(s) of palatal seam disintegration. Current understanding of palatal seam disintegration suggests epithelial–mesenchymal transition and/or programmed cell death as two most common mechanisms of MES disintegration. In this review, I discuss those two mechanisms and the differences between them. PMID:18629865

Novel Bioinformatics-Based Approach for Proteomic Biomarkers Prediction of Calpain-2 & Caspase-3 Protease Fragmentation: Application to βII-Spectrin Protein

NASA Astrophysics Data System (ADS)

El-Assaad, Atlal; Dawy, Zaher; Nemer, Georges; Kobeissy, Firas

2017-01-01

The crucial biological role of proteases has been visible with the development of degradomics discipline involved in the determination of the proteases/substrates resulting in breakdown-products (BDPs) that can be utilized as putative biomarkers associated with different biological-clinical significance. In the field of cancer biology, matrix metalloproteinases (MMPs) have shown to result in MMPs-generated protein BDPs that are indicative of malignant growth in cancer, while in the field of neural injury, calpain-2 and caspase-3 proteases generate BDPs fragments that are indicative of different neural cell death mechanisms in different injury scenarios. Advanced proteomic techniques have shown a remarkable progress in identifying these BDPs experimentally. In this work, we present a bioinformatics-based prediction method that identifies protease-associated BDPs with high precision and efficiency. The method utilizes state-of-the-art sequence matching and alignment algorithms. It starts by locating consensus sequence occurrences and their variants in any set of protein substrates, generating all fragments resulting from cleavage. The complexity exists in space O(mn) as well as in O(Nmn) time, where N, m, and n are the number of protein sequences, length of the consensus sequence, and length per protein sequence, respectively. Finally, the proposed methodology is validated against βII-spectrin protein, a brain injury validated biomarker.

Transcriptional and epigenetic control in mouse pluripotency: lessons from in vivo and in vitro studies.

PubMed

Habibi, Ehsan; Stunnenberg, Hendrik G

2017-10-01

Pluripotent cells were first derived from mouse blastocysts several decades ago. Since then, our knowledge of the molecular events that occur in the pre-implantation embryo has been vastly progressing. The emergence of epigenetics has revolutionized stem cell and developmental biology and further deepened our understanding of the underlying molecular mechanisms controlling the early embryo development. In particular, the emergence of massive parallel sequencing technologies has opened new avenues and became indispensable tools in modern biology. Additionally, development of new and exciting techniques for genome manipulation (TALEN and CRISPR/Cas9) and in vivo imaging provide unique opportunities to perturb and trace biological systems at very high resolution. Finally, recent single-cell - omics combined with sophisticated computational methodologies allow accurate, quantitative measurements for deconvolution of cellular variation in complex cell populations. Collectively, these achievements enabled the detailed characterization and monitoring of various cell states and trajectories during early stages of embryonic development. Here we review recent studies of the transcriptional and epigenetic changes during very early stages of mouse embryo development and compare these with pluripotent cells grown in vitro under different culture conditions. We discuss whether the in vitro cell states have an 'epi-phenocopy' in the embryo and refine our understanding of the circuitries controlling pluripotency and lineage commitment during early stages of mouse development. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Biology Division progress report, October 1, 1978-May 31, 1980. [Lead abstract

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

Not Available

Separate abstracts were prepared for each of the four sections into which this progress report has been divided. The report also contains sections related to interdivision activities and educational activities. (ERB)

[Intracranial plasmocytomas: biology, diagnosis, and treatment].

PubMed

Belov, A I; Gol'bin, D A

2006-01-01

Intracranial plasmocytomas are a rare abnormality in a neurosurgeon's practice. The plasmocytomas may originate from the skull bones or soft tissue intracranial structures; they may be solitary or occur as a manifestation of multiple myeloma, this type being typical of most intracranial plasmocytomas. Progression of solitary plasmocytoma to multiple myeloma is observed in a number of cases. Preoperative diagnosis involves computed tomography or magnetic resonance imaging; angiography is desirable. The final diagnosis of plasmocytoma is chiefly based on a morphological study. Special immunohistochemical studies yield very promising results; these are likely to be of high prognostic value. Intracranial plasmocytomas require a differential approach and a meticulous examination since the presence or absence of multiple myeloma radically affects prognosis. There are well-defined predictors; however, it is appropriate that craniobasal plasmocytomas show a worse prognosis than plasmocytomas of the skull vault and more commonly progress to multiple myeloma. Plasmocytomas respond to radiotherapy very well. The gold standard of treatment for plasmocytoma is its total removal and adjuvant radiation therapy; however, there is evidence for good results when it is partially removed and undergoes radiotherapy or after radical surgery without subsequent radiation. The role of chemotherapy has not been defined today.

Antimicrobial graphene family materials: Progress, advances, hopes and fears.

PubMed

Lukowiak, Anna; Kedziora, Anna; Strek, Wieslaw

2016-10-01

Graphene-based materials have become very popular bionanotechnological instruments in the last few years. Since 2010, the graphene family materials have been recognized as worthy of attention due to its antimicrobial properties. Functionalization of graphene (or rather graphene oxide) surface creates the possibilities to obtain efficient antimicrobial agents. In this review, progress and advances in this field in the last few years are described and discussed. Special attention is devoted to materials based on graphene oxide in which specifically selected components significantly modify biological activity of this carbon structure. Short introduction concerns the physicochemical properties of the graphene family materials. In the section on antimicrobial properties, proposed mechanisms of activity against microorganisms are given showing enhanced action of nanocomposites also under light irradiation (photoinduced activity). Another important feature, i.e. toxicity against eukaryotic cells, is presented with up-to-date data. Taking into account all the information on the properties of the described materials and usefulness of the graphene family as antimicrobial agents, hopes and fears concerning their application are discussed. Finally, some examples of promising usage in medicine and other fields, e.g. in phytobiology and water remediation, are shown. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluating Chagas disease progression and cure through blood-derived biomarkers: a systematic review.

PubMed

Requena-Méndez, Ana; López, Manuel Carlos; Angheben, Andrea; Izquierdo, Luis; Ribeiro, Isabela; Pinazo, Maria-Jesús; Gascon, Joaquim; Muñoz, José

2013-09-01

This article reviews the usefulness of various types of blood-derived biomarkers that are currently being studied to predict the progression of Chagas disease in patients with the indeterminate form, to assess the efficacy of antiparasitic drugs and to identify early cardiac and gastrointestinal damage. The authors used a search strategy based on MEDLINE, Cochrane Library Register for systematic review, EmBase, Global Health and LILACS databases. Out of 1716 screened articles, only 166 articles were eligible for final inclusion. The authors classified the biomarkers according to their biochemical structure and primary biological activity in four groups: i) markers of inflammation and cellular injury, ii) metabolic biomakers, iii) prothrombotic biomarkers and iv) markers derived from specific antigens of the parasite. Several potential biomarkers might have clinical potential for the detection of early cardiopathy. Such capacity is imperative in order to detect high-risk patients who require intensive monitoring and earlier therapy. Prospective studies with longer follow-ups are needed for the appraisal of biomarkers assessing clinical or microbiological cure after therapy. At the same time, studies evaluating more than one biomarker are useful to compare the efficacy among them given the lack of a recognized gold standard.

A comprehensive view of the web-resources related to sericulture

PubMed Central

Singh, Deepika; Chetia, Hasnahana; Kabiraj, Debajyoti; Sharma, Swagata; Kumar, Anil; Sharma, Pragya; Deka, Manab; Bora, Utpal

2016-01-01

Recent progress in the field of sequencing and analysis has led to a tremendous spike in data and the development of data science tools. One of the outcomes of this scientific progress is development of numerous databases which are gaining popularity in all disciplines of biology including sericulture. As economically important organism, silkworms are studied extensively for their numerous applications in the field of textiles, biomaterials, biomimetics, etc. Similarly, host plants, pests, pathogens, etc. are also being probed to understand the seri-resources more efficiently. These studies have led to the generation of numerous seri-related databases which are extremely helpful for the scientific community. In this article, we have reviewed all the available online resources on silkworm and its related organisms, including databases as well as informative websites. We have studied their basic features and impact on research through citation count analysis, finally discussing the role of emerging sequencing and analysis technologies in the field of seri-data science. As an outcome of this review, a web portal named SeriPort, has been created which will act as an index for the various sericulture-related databases and web resources available in cyberspace. Database URL: http://www.seriport.in/ PMID:27307138

How I treat smoldering multiple myeloma

PubMed Central

Landgren, Ola

2014-01-01

Smoldering myeloma is a heterogeneous clinical entity where a subset of patients has an indolent course of disease that mimics monoclonal gammopathy of undermined significance, whereas others have a more aggressive course that has been described as “early myeloma.” It is defined as either serum M-protein ≥3 g/L or ≥10% monoclonal plasma cells in the bone marrow. There are currently no molecular factors to differentiate risks of progression for these patients. Current recommendations of therapy continue to be patient observation or patient enrollment in clinical trials. However, new definitions of active multiple myeloma recently agreed upon by the International Myeloma Working Group may alter the timing of therapy. On the basis of emerging data of therapy in these patients, it seems reasonable to believe that future recommendations for therapy of patients with smoldering myeloma will become an increasingly important topic. In this article, we review the current knowledge of this disease and risk factors associated with progression. We also examine biological insights and alterations that occur in the tumor clone and the surrounding bone marrow niche. Finally, we review clinical trials that have been performed in these patients and provide recommendations for follow-up of patients with this unique disease entity. PMID:25298034

An "elite hacker": breast tumors exploit the normal microenvironment program to instruct their progression and biological diversity.

PubMed

Boudreau, Aaron; van't Veer, Laura J; Bissell, Mina J

2012-01-01

The year 2011 marked the 40 year anniversary of Richard Nixon signing the National Cancer Act, thus declaring the beginning of the "War on Cancer" in the United States. Whereas we have made tremendous progress toward understanding the genetics of tumors in the past four decades, and in developing enabling technology to dissect the molecular underpinnings of cancer at unprecedented resolution, it is only recently that the important role of the stromal microenvironment has been studied in detail. Cancer is a tissue-specific disease, and it is becoming clear that much of what we know about breast cancer progression parallels the biology of the normal breast differentiation, of which there is still much to learn. In particular, the normal breast and breast tumors share molecular, cellular, systemic and microenvironmental influences necessary for their progression. It is therefore enticing to consider a tumor to be a "rogue hacker"--one who exploits the weaknesses of a normal program for personal benefit. Understanding normal mammary gland biology and its "security vulnerabilities" may thus leave us better equipped to target breast cancer. In this review, we will provide a brief overview of the heterotypic cellular and molecular interactions within the microenvironment of the developing mammary gland that are necessary for functional differentiation, provide evidence suggesting that similar biology--albeit imbalanced and exaggerated--is observed in breast cancer progression particularly during the transition from carcinoma in situ to invasive disease. Lastly we will present evidence suggesting that the multigene signatures currently used to model cancer heterogeneity and clinical outcome largely reflect signaling from a heterogeneous microenvironment-a recurring theme that could potentially be exploited therapeutically.

Resistance may be an important mechanism by which marine microbes respond to environmental toxicants*1

NASA Astrophysics Data System (ADS)

Capriulo, Gerard M.; Flanzenbaum, Jeffrey; Wurster, Charles F.; Rowland, R. George

1983-11-01

The hypothesis, that at least certain marine microbial organisms respond to toxic stress by the development of resistance, was tested using the hypotric marine ciliate Euplotes vannus Muller as the test organism. Resistance to polychlorinated biphenyls (PCB, Aroclor 1254) was developed in E. vannus by exposing the animals to progressively higher PCB concentrations during a period of several months. The resistance to PCB persisted for at least 80 days (greater than 40 generations) after final exposure. This suggests either that genetic selection or persistent (lasting over many cell division cycles) phenotypic trait modification, possibly in the form of Dauermodification, had occurred. If resistance were widespread among marine microbial organisms in polluted environments it would be an important consideration in evaluating the long-term biological impact of both natural and man-induced chemical stress.

Melanocytic nevi and melanoma: unraveling a complex relationship

PubMed Central

Damsky, WE; Bosenberg, M

2018-01-01

Approximately 33% of melanomas are derived directly from benign, melanocytic nevi. Despite this, the vast majority of melanocytic nevi, which typically form as a result of BRAFV600E-activating mutations, will never progress to melanoma. Herein, we synthesize basic scientific insights and data from mouse models with common observations from clinical practice to comprehensively review melanocytic nevus biology. In particular, we focus on the mechanisms by which growth arrest is established after BRAFV600E mutation. Means by which growth arrest can be overcome and how melanocytic nevi relate to melanoma are also considered. Finally, we present a new conceptual paradigm for understanding the growth arrest of melanocytic nevi in vivo termed stable clonal expansion. This review builds upon the canonical hypothesis of oncogene-induced senescence in growth arrest and tumor suppression in melanocytic nevi and melanoma. PMID:28604751

Chimeric Antigen Receptor-Redirected T cells return to the bench

PubMed Central

Geldres, Claudia; Savoldo, Barbara; Dotti, Gianpietro

2016-01-01

While the clinical progress of chimeric antigen receptor T cell (CAR-T) immunotherapy has garnered attention to the field, our understanding of the biology of these chimeric molecules is still emerging. Our aim within this review is to bring to light the mechanistic understanding of these multi-modular receptors and how these individual components confer particular properties to CAR-Ts. In addition, we will discuss extrinsic factors that can be manipulated to influence CAR-T performance such as choice of cellular population, culturing conditions and additional modifications that enhance their activity particularly in solid tumors. Finally, we will also consider the emerging toxicity associated with CAR-Ts. By breaking apart the CAR and examining the role of each piece, we can build a better functioning cellular vehicle for optimized treatment of cancer patients. PMID:26797495

Exploring the Spatiotemporal Organization of Membrane Proteins in Living Plant Cells.

PubMed

Wang, Li; Xue, Yiqun; Xing, Jingjing; Song, Kai; Lin, Jinxing

2018-04-29

Plasma membrane proteins have important roles in transport and signal transduction. Deciphering the spatiotemporal organization of these proteins provides crucial information for elucidating the links between the behaviors of different molecules. However, monitoring membrane proteins without disrupting their membrane environment remains difficult. Over the past decade, many studies have developed single-molecule techniques, opening avenues for probing the stoichiometry and interactions of membrane proteins in their native environment by providing nanometer-scale spatial information and nanosecond-scale temporal information. In this review, we assess recent progress in the development of labeling and imaging technology for membrane protein analysis. We focus in particular on several single-molecule techniques for quantifying the dynamics and assembly of membrane proteins. Finally, we provide examples of how these new techniques are advancing our understanding of the complex biological functions of membrane proteins.

Semi-Automated Curation Allows Causal Network Model Building for the Quantification of Age-Dependent Plaque Progression in ApoE-/- Mouse.

PubMed

Szostak, Justyna; Martin, Florian; Talikka, Marja; Peitsch, Manuel C; Hoeng, Julia

2016-01-01

The cellular and molecular mechanisms behind the process of atherosclerotic plaque destabilization are complex, and molecular data from aortic plaques are difficult to interpret. Biological network models may overcome these difficulties and precisely quantify the molecular mechanisms impacted during disease progression. The atherosclerosis plaque destabilization biological network model was constructed with the semiautomated curation pipeline, BELIEF. Cellular and molecular mechanisms promoting plaque destabilization or rupture were captured in the network model. Public transcriptomic data sets were used to demonstrate the specificity of the network model and to capture the different mechanisms that were impacted in ApoE -/- mouse aorta at 6 and 32 weeks. We concluded that network models combined with the network perturbation amplitude algorithm provide a sensitive, quantitative method to follow disease progression at the molecular level. This approach can be used to investigate and quantify molecular mechanisms during plaque progression.

Population Biology, Conservation Biology, and the Future of Humanity.

ERIC Educational Resources Information Center

Ehrlich, Paul R.

1987-01-01

Recounts some of the progress that has been made in the field of population biology. Presents some of the important advances made in the field, along with some of their applications to societal problems. Calls for more cooperation between population scientists and social scientists, and more environmental education for the public. (TW)

Developing Information Fluency in Introductory Biology Students in the Context of an Investigative Laboratory

ERIC Educational Resources Information Center

Lindquester, Gary J.; Burks, Romi L.; Jaslow, Carolyn R.

2005-01-01

Students of biology must learn the scientific method for generating information in the field. Concurrently, they should learn how information is reported and accessed. We developed a progressive set of exercises for the undergraduate introductory biology laboratory that combine these objectives. Pre- and postassessments of approximately 100…

Bone effects of biologic drugs in rheumatoid arthritis.

PubMed

Corrado, Addolorata; Neve, Anna; Maruotti, Nicola; Cantatore, Francesco Paolo

2013-01-01

Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNF α , IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNF α , IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

Development and Assessment of a Horizontally Integrated Biological Sciences Course Sequence for Pharmacy Education

PubMed Central

Wright, Nicholas J.D.; Alston, Gregory L.

2015-01-01

Objective. To design and assess a horizontally integrated biological sciences course sequence and to determine its effectiveness in imparting the foundational science knowledge necessary to successfully progress through the pharmacy school curriculum and produce competent pharmacy school graduates. Design. A 2-semester course sequence integrated principles from several basic science disciplines: biochemistry, molecular biology, cellular biology, anatomy, physiology, and pathophysiology. Each is a 5-credit course taught 5 days per week, with 50-minute class periods. Assessment. Achievement of outcomes was determined with course examinations, student lecture, and an annual skills mastery assessment. The North American Pharmacist Licensure Examination (NAPLEX) results were used as an indicator of competency to practice pharmacy. Conclusion. Students achieved course objectives and program level outcomes. The biological sciences integrated course sequence was successful in providing students with foundational basic science knowledge required to progress through the pharmacy program and to pass the NAPLEX. The percentage of the school’s students who passed the NAPLEX was not statistically different from the national percentage. PMID:26430276

Inferring Causes of Biological Impairment in the Clear Fork Watershed, West Virginia (Final)

EPA Science Inventory

EPA announced the availability of the final report, Inferring Causes of Biological Impairment in the Clear Fork Watershed, West Virginia. This study illustrates a causal assessment in a watershed using the US EPA stressor identification process described on the www.epa....

Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology (Final Report)

EPA Science Inventory

EPA announced the release of the final report, Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology. This report describes new approaches that are faster, less resource intensive, and more robust that can help ...

21 CFR 640.103 - The final product.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false The final product. 640.103 Section 640.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... manufacturer by the Director, Center for Biologics Evaluation and Research, Food and Drug Administration. [38...

21 CFR 640.103 - The final product.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 7 2011-04-01 2010-04-01 true The final product. 640.103 Section 640.103 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... manufacturer by the Director, Center for Biologics Evaluation and Research, Food and Drug Administration. [38...

The application of advanced oxidation technologies to the treatment of effluents from the pulp and paper industry: a review.

PubMed

Hermosilla, Daphne; Merayo, Noemí; Gascó, Antonio; Blanco, Ángeles

2015-01-01

The paper industry is adopting zero liquid effluent technologies to reduce freshwater use and meet environmental regulations, which implies closure of water circuits and the progressive accumulation of pollutants that must be removed before water reuse and final wastewater discharge. The traditional water treatment technologies that are used in paper mills (such as dissolved air flotation or biological treatment) are not able to remove recalcitrant contaminants. Therefore, advanced water treatment technologies, such as advanced oxidation processes (AOPs), are being included in industrial wastewater treatment chains aiming to either improve water biodegradability or its final quality. A comprehensive review of the current state of the art regarding the use of AOPs for the treatment of the organic load of effluents from the paper industry is herein addressed considering mature and emerging treatments for a sustainable water use in this sector. Wastewater composition, which is highly dependent on the raw materials being used in the mills, the selected AOP itself, and its combination with other technologies, will determine the viability of the treatment. In general, all AOPs have been reported to achieve good organic removal efficiencies (COD removal >40%, and about an extra 20% if AOPs are combined with biological stages). Particularly, ozonation has been the most extensively reported and successfully implemented AOP at an industrial scale for effluent treatment or reuse within pulp and paper mills, although Fenton processes (photo-Fenton particularly) have actually addressed better oxidative results (COD removal ≈ 65-75%) at a lab scale, but still need further development at a large scale.

Empirical Validation of a Modern Genetics Progression Web for College Biology Students

ERIC Educational Resources Information Center

Todd, Amber; Romine, William L.

2017-01-01

Research in learning progressions (LPs) has been essential towards building understanding of how students' ideas change over time. There has been little work, however, into how ideas between separate but related constructs within a multi-faceted LP relate. The purpose of this paper is to elaborate on the idea of "progression webs" to…

Development and Validation of the Learning Progression-Based Assessment of Modern Genetics in a High School Context

ERIC Educational Resources Information Center

Todd, Amber; Romine, William L.; Cook Whitt, Katahdin

2017-01-01

We describe the development, validation, and use of the "Learning Progression-Based Assessment of Modern Genetics" (LPA-MG) in a high school biology context. Items were constructed based on a current learning progression framework for genetics (Shea & Duncan, 2013; Todd & Kenyon, 2015). The 34-item instrument, which was tied to…

Molecular Biology of Pseudorabies Virus: Impact on Neurovirology and Veterinary Medicine

PubMed Central

Pomeranz, Lisa E.; Reynolds, Ashley E.; Hengartner, Christoph J.

2005-01-01

Pseudorabies virus (PRV) is a herpesvirus of swine, a member of the Alphaherpesvirinae subfamily, and the etiological agent of Aujeszky's disease. This review describes the contributions of PRV research to herpesvirus biology, neurobiology, and viral pathogenesis by focusing on (i) the molecular biology of PRV, (ii) model systems to study PRV pathogenesis and neurovirulence, (iii) PRV transsynaptic tracing of neuronal circuits, and (iv) veterinary aspects of pseudorabies disease. The structure of the enveloped infectious particle, the content of the viral DNA genome, and a step-by-step overview of the viral replication cycle are presented. PRV infection is initiated by binding to cellular receptors to allow penetration into the cell. After reaching the nucleus, the viral genome directs a regulated gene expression cascade that culminates with viral DNA replication and production of new virion constituents. Finally, progeny virions self-assemble and exit the host cells. Animal models and neuronal culture systems developed for the study of PRV pathogenesis and neurovirulence are discussed. PRV serves as a self-perpetuating transsynaptic tracer of neuronal circuitry, and we detail the original studies of PRV circuitry mapping, the biology underlying this application, and the development of the next generation of tracer viruses. The basic veterinary aspects of pseudorabies management and disease in swine are discussed. PRV infection progresses from acute infection of the respiratory epithelium to latent infection in the peripheral nervous system. Sporadic reactivation from latency can transmit PRV to new hosts. The successful management of PRV disease has relied on vaccination, prevention, and testing. PMID:16148307

Test-enhanced learning: the potential for testing to promote greater learning in undergraduate science courses.

PubMed

Brame, Cynthia J; Biel, Rachel

2015-01-01

Testing within the science classroom is commonly used for both formative and summative assessment purposes to let the student and the instructor gauge progress toward learning goals. Research within cognitive science suggests, however, that testing can also be a learning event. We present summaries of studies that suggest that repeated retrieval can enhance long-term learning in a laboratory setting; various testing formats can promote learning; feedback enhances the benefits of testing; testing can potentiate further study; and benefits of testing are not limited to rote memory. Most of these studies were performed in a laboratory environment, so we also present summaries of experiments suggesting that the benefits of testing can extend to the classroom. Finally, we suggest opportunities that these observations raise for the classroom and for further research. © 2015 C. J. Brame and R. Biel. CBE—Life Sciences Education © 2015 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

What can we learn about lipoprotein metabolism and coronary heart disease from studying rare variants?

PubMed

Jeff, Janina M; Peloso, Gina M; Do, Ron

2016-04-01

Rare variant association studies (RVAS) target the class of genetic variation with frequencies less than 1%. Recently, investigators have used exome sequencing in RVAS to identify rare alleles responsible for Mendelian diseases but have experienced greater difficulty discovering such alleles for complex diseases. In this review, we describe what we have learned about lipoprotein metabolism and coronary heart disease through the conduct of RVAS. Rare protein-altering genetic variation can provide important insights that are not as easily attainable from common variant association studies. First, RVAS can facilitate gene discovery by identifying novel rare protein-altering variants in specific genes that are associated with disease. Second, rare variant associations can provide supportive evidence for putative drug targets for novel therapies. Finally, rare variants can uncover new pathways and reveal new biologic mechanisms. The field of human genetics has already made tremendous progress in understanding lipoprotein metabolism and the causes of coronary heart disease in the context of rare variants. As next generation sequencing becomes more cost-effective, RVAS with larger sample sizes will be conducted. This will lead to more novel rare variant discoveries and the translation of genomic data into biological knowledge and clinical insights for cardiovascular disease.

Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

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

Xia, Jing; Rocke, David M.; Perry, George

In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

A review of digital microfluidics as portable platforms for lab-on a-chip applications.

PubMed

Samiei, Ehsan; Tabrizian, Maryam; Hoorfar, Mina

2016-07-07

Following the development of microfluidic systems, there has been a high tendency towards developing lab-on-a-chip devices for biochemical applications. A great deal of effort has been devoted to improve and advance these devices with the goal of performing complete sets of biochemical assays on the device and possibly developing portable platforms for point of care applications. Among the different microfluidic systems used for such a purpose, digital microfluidics (DMF) shows high flexibility and capability of performing multiplex and parallel biochemical operations, and hence, has been considered as a suitable candidate for lab-on-a-chip applications. In this review, we discuss the most recent advances in the DMF platforms, and evaluate the feasibility of developing multifunctional packages for performing complete sets of processes of biochemical assays, particularly for point-of-care applications. The progress in the development of DMF systems is reviewed from eight different aspects, including device fabrication, basic fluidic operations, automation, manipulation of biological samples, advanced operations, detection, biological applications, and finally, packaging and portability of the DMF devices. Success in developing the lab-on-a-chip DMF devices will be concluded based on the advances achieved in each of these aspects.

Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism[S

PubMed Central

Palczewski, Grzegorz; Widjaja-Adhi, M. Airanthi K.; Amengual, Jaume; Golczak, Marcin; von Lintig, Johannes

2016-01-01

Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health. However, knowledge about their biological action and the consequences of their dietary accumulation in mammals is limited. Progress in this research field is limited by the expeditious metabolism of carotenoids in rodents and the confounding production of apocarotenoid signaling molecules. Herein, we established a mouse model lacking the enzymes responsible for carotenoid catabolism and apocarotenoid production, fed on either a β-carotene- or a zeaxanthin-enriched diet. Applying a genome wide microarray analysis, we assessed the effects of the parent carotenoids on the liver transcriptome. Our analysis documented changes in pathways for liver lipid metabolism and mitochondrial respiration. We biochemically defined these effects, and observed that β-carotene accumulation resulted in an elevation of liver triglycerides and liver cholesterol, while zeaxanthin accumulation increased serum cholesterol levels. We further show that carotenoids were predominantly transported within HDL particles in the serum of mice. Finally, we provide evidence that carotenoid accumulation influenced whole-body respiration and energy expenditure. Thus, we observed that accumulation of parent carotenoids interacts with lipid metabolism and that structurally related carotenoids display distinct biological functions in mammals. PMID:27389691

Differential Network Analyses of Alzheimer’s Disease Identify Early Events in Alzheimer’s Disease Pathology

DOE PAGES

Xia, Jing; Rocke, David M.; Perry, George; ...

2014-01-01

In late-onset Alzheimer’s disease (AD), multiple brain regions are not affected simultaneously. Comparing the gene expression of the affected regions to identify the differences in the biological processes perturbed can lead to greater insight into AD pathogenesis and early characteristics. We identified differentially expressed (DE) genes from single cell microarray data of four AD affected brain regions: entorhinal cortex (EC), hippocampus (HIP), posterior cingulate cortex (PCC), and middle temporal gyrus (MTG). We organized the DE genes in the four brain regions into region-specific gene coexpression networks. Differential neighborhood analyses in the coexpression networks were performed to identify genes with lowmore » topological overlap (TO) of their direct neighbors. The low TO genes were used to characterize the biological differences between two regions. Our analyses show that increased oxidative stress, along with alterations in lipid metabolism in neurons, may be some of the very early events occurring in AD pathology. Cellular defense mechanisms try to intervene but fail, finally resulting in AD pathology as the disease progresses. Furthermore, disease annotation of the low TO genes in two independent protein interaction networks has resulted in association between cancer, diabetes, renal diseases, and cardiovascular diseases.« less

Genetic Bases of Stuttering: The State of the Art, 2011

PubMed Central

Kraft, Shelly Jo; Yairi, Ehud

2011-01-01

Objective The literature on the genetics of stuttering is reviewed with special reference to the historical development from psychosocial explanations leading up to current biological research of gene identification. Summary A gradual progression has been made from the early crude methods of counting percentages of stuttering probands who have relatives who stutter to recent studies using entire genomes of DNA collected from each participant. Despite the shortcomings of some early studies, investigators have accumulated a substantial body of data showing a large presence of familial stuttering. This encouraged more refined research in the form of twin studies. Concordance rates among twins were sufficiently high to lend additional support to the genetic perspective of stuttering. More sophisticated aggregation studies and segregation analyses followed, producing data that matched recognized genetic models, providing the final ‘go ahead’ to proceed from the behavior/statistical genetics into the sphere of biological genetics. Recent linkage and association studies have begun to reveal contributing genes to the disorder. Conclusion No definitive findings have been made regarding which transmission model, chromosomes, genes, or sex factors are involved in the expression of stuttering in the population at large. Future research and clinical implications are discussed. PMID:22067705

Biologic resurfacing of the patella: current status.

PubMed

Scapinelli, Raphaele; Aglietti, Paolo; Baldovin, Marino; Giron, Francesco; Teitge, Robert

2002-07-01

The techniques of biologic resurfacing of the patella, like other joint surfaces, are still evolving. Currently none of them is free from criticism. In this regard it is our hope that progress in the basic science will offer in the near future new and more optimistic therapeutic possibilities (i.e., the restoration of a reparative cartilage that is structurally and functionally comparable to the native one). The greater expectancies come perhaps from the present experimental investigations about the combined use of tissue-engineered implants embedded with staminal cells and growth factors. Many problems remain to be solved, however, before reliable applicability in humans. From a general point of view, stem cells obtained from various sources (e.g., adult bone marrow, umbilical cord) offer the same finalities as the embryonic stem cells, without the ethical obstacles related to the latter. Therefore, it may be that restoration of part or all of the articular surface of a joint will be possible by way of these mesenchymal progenitors that have the ability to differentiate into the chondrogenic and osteogenic lines, which is required for the restoration of the various layers of a normal articular cartilage and subchondral bone.

MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer.

PubMed

Canu, Valeria; Sacconi, Andrea; Lorenzon, Laura; Biagioni, Francesca; Lo Sardo, Federica; Diodoro, Maria Grazia; Muti, Paola; Garofalo, Alfredo; Strano, Sabrina; D'Errico, Antonietta; Grazi, Gian Luca; Cioce, Mario; Blandino, Giovanni

2017-05-02

There is high need of novel diagnostic and prognostic tools for tumors of the digestive system, such as gastric cancer and cholangiocarcinoma. We recently found that miR-204 was deeply downregulated in gastric cancer tissues. Here we investigated whether this was common to other tumors of the digestive system and whether this elicited a miR-204-dependent gene target signature, diagnostically and therapeutically relevant. Finally, we assessed the contribution of the identified target genes to the cell cycle progression and clonogenicity of gastric cancer and cholangiocarcinoma cell lines. We employed quantitative PCR and Affymetrix profiling for gene expression studies. In silico analysis aided us to identifying a miR-204 target signature in publicly available databases (TGCA). We employed transient transfection experiments, clonogenic assays and cell cycle profiling to evaluate the biological consequences of miR-204 perturbation. We identified a novel miR-204 gene target signature perturbed in gastric cancer and in cholangiocarcinoma specimens. We validated its prognostic relevance and mechanistically addressed its biological relevance in GC and CC cell lines. We suggest that restoring the physiological levels of miR-204 in some gastrointestinal cancers might be exploited therapeutically.

Advantages of Structure-Based Drug Design Approaches in Neurological Disorders

PubMed Central

Aarthy, Murali; Panwar, Umesh; Selvaraj, Chandrabose; Singh, Sanjeev Kumar

2017-01-01

Objective: The purpose of the review is to portray the theoretical concept on neurological disorders from research data. Background: The freak changes in chemical response of nerve impulse causes neurological disorders. The research evidence of the effort done in the older history suggests that the biological drug targets and their effective feature with responsive drugs could be valuable in promoting the future development of health statistics structure for improved treatment for curing the nervous disorders. Methods: In this review, we summarized the most iterative theoretical concept of structure based drug design approaches in various neurological disorders to unfathomable understanding of reported information for future drug design and development. Results: On the premise of reported information we analyzed the model of theoretical drug designing process for understanding the mechanism and pathology of the neurological diseases which covers the development of potentially effective inhibitors against the biological drug targets. Finally, it also suggests the management and implementation of the current treatment in improving the human health system behaviors. Conclusion: With the survey of reported information we concluded the development strategies of diagnosis and treatment against neurological diseases which leads to supportive progress in the drug discovery. PMID:28042767

Improving Toxicity Assessment of Pesticide Mixtures: The Use of Polar Passive Sampling Devices Extracts in Microalgae Toxicity Tests

PubMed Central

Kim Tiam, Sandra; Fauvelle, Vincent; Morin, Soizic; Mazzella, Nicolas

2016-01-01

Complexity of contaminants exposure needs to be taking in account for an appropriate evaluation of risks related to mixtures of pesticides released in the ecosystems. Toxicity assessment of such mixtures can be made through a variety of toxicity tests reflecting different level of biological complexity. This paper reviews the recent developments of passive sampling techniques for polar compounds, especially Polar Organic Chemical Integrative Samplers (POCIS) and Chemcatcher® and the principal assessment techniques using microalgae in laboratory experiments. The progresses permitted by the coupled use of such passive samplers and ecotoxicology testing as well as their limitations are presented. Case studies combining passive sampling devices (PSD) extracts and toxicity assessment toward microorganisms at different biological scales from single organisms to communities level are presented. These case studies, respectively, aimed (i) at characterizing the “toxic potential” of waters using dose-response curves, and (ii) at performing microcosm experiments with increased environmental realism in the toxicant exposure in term of cocktail composition and concentration. Finally perspectives and limitations of such approaches for future applications in the area of environmental risk assessment are discussed. PMID:27667986

The Many Facets of Metzincins and Their Endogenous Inhibitors: Perspectives on Ovarian Cancer Progression

PubMed Central

Escalona, Ruth M.; Chan, Emily; Kannourakis, George; Findlay, Jock K.; Ahmed, Nuzhat

2018-01-01

Approximately sixty per cent of ovarian cancer patients die within the first five years of diagnosis due to recurrence associated with chemoresistance. The metzincin family of metalloproteinases is enzymes involved in matrix remodeling in response to normal physiological changes and diseased states. Recently, there has been a mounting awareness of these proteinases and their endogenous inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), as superb modulators of cellular communication and signaling regulating key biological processes in cancer progression. This review investigates the role of metzincins and their inhibitors in ovarian cancer. We propose that understanding the metzincins and TIMP biology in ovarian cancer may provide valuable insights in combating ovarian cancer progression and chemoresistance-mediated recurrence in patients. PMID:29393911

Biological and Clinical Implications of Comorbidities in Parkinson’s Disease

PubMed Central

Santiago, Jose A.; Bottero, Virginie; Potashkin, Judith A.

2017-01-01

A wide spectrum of comorbidities has been associated with Parkinson’s disease (PD), a progressive neurodegenerative disease that affects more than seven million people worldwide. Emerging evidence indicates that chronic diseases including diabetes, depression, anemia and cancer may be implicated in the pathogenesis and progression of PD. Recent epidemiological studies suggest that some of these comorbidities may increase the risk of PD and precede the onset of motor symptoms. Further, drugs to treat diabetes and cancer have elicited neuroprotective effects in PD models. Nonetheless, the mechanisms underlying the occurrence of these comorbidities remain elusive. Herein, we discuss the biological and clinical implications of comorbidities in the pathogenesis, progression, and clinical management, with an emphasis on personalized medicine applications for PD. PMID:29255414

Recent progress in chemical and chemoenzymatic synthesis of carbohydrates.

PubMed

Muthana, Saddam; Cao, Hongzhi; Chen, Xi

2009-12-01

The important roles that carbohydrates play in biological processes and their potential application in diagnosis, therapeutics, and vaccine development have made them attractive synthetic targets. Despite ongoing challenges, tremendous progresses have been made in recent years for the synthesis of carbohydrates. The chemical glycosylation methods have become more sophisticated and the synthesis of oligosaccharides has become more predictable. Simplified one-pot glycosylation strategy and automated synthesis are increasingly used to obtain biologically important glycans. On the other hand, chemoenzymatic synthesis continues to be a powerful alternative for obtaining complex carbohydrates. This review highlights recent progress in chemical and chemoenzymatic synthesis of carbohydrates with a particular focus on the methods developed for the synthesis of oligosaccharides, polysaccharides, glycolipids, and glycosylated natural products.

Recent Progress in Chemical and Chemoenzymatic Synthesis of Carbohydrates

PubMed Central

Muthana, Saddam; Cao, Hongzhi; Chen, Xi

2011-01-01

Summary The important roles that carbohydrates play in biological processes and their potential application in diagnosis, therapeutics, and vaccine development have made them attractive synthetic targets. Despite ongoing challenges, tremendous progresses have been made in recent years for the synthesis of carbohydrates. The chemical glycosylation methods have become more sophisticated and the synthesis of oligosaccharides has become more predictable. Simplified one-pot glycosylation strategy and automated synthesis are increasingly used to obtain biologically important glycans. On the other hand, chemoenzymatic synthesis continues to be a powerful alternative for obtaining complex carbohydrates. This review highlights recent progress in chemical and chemoenzymatic synthesis of carbohydrates with a particular focus on the methods developed for the synthesis of oligosaccharides, polysaccharides, glycolipids, and glycosylated natural products. PMID:19833544

New measurements for hadrontherapy and space radiation: biology

NASA Technical Reports Server (NTRS)

Blakely, E. A.

2001-01-01

The dual goals of optimizing clinical efficacy of hadrontherapy and determining radiation risk estimates for space research have intersected to a common focus for investigation of the biological effects of charged particles. This paper briefly highlights recent international progress at accelerator facilities engaged in both biological and clinical studies of the effects of particle beams, primarily protons, carbon and iron ions. Basic mechanisms of molecular, cellular and tissue responses continue under investigation for radiations with a range of ionization densities. Late normal tissue effects, including the risk of cancer in particular, are of importance for both research fields. International cooperation has enhanced the rate of progress as evidenced by recent publications. Specific areas of biomedical research related to the biological radiotoxicity of critical organs (especially the central nervous system), individual radiosensitivities to radiation carcinogenesis, and the analysis of effects in mixed radiation fields still require more research. Recommendations for addressing these issues are made.

Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops

PubMed Central

Mullins, Caitlin; Fishell, Gord

2017-01-01

Understanding the mechanisms underlying autism spectrum disorders (ASD) is a challenging goal. Here we review recent progress on several fronts, including genetics, proteomics, biochemistry and electrophysiology, that raise motivation for forming a viable pathophysiological hypothesis. In place of a traditionally unidirectional progression, we put forward a framework that extends homeostatic hypotheses by explicitly emphasizing autoregulatory feedback loops and known synaptic biology. The regulated biological feature can be neuronal electrical activity, the collective strength of synapses onto a dendritic branch, the local concentration of a signaling molecule, or the relative strengths of synaptic excitation and inhibition. The sensor of the biological variable (which we have termed the homeostat) engages mechanisms that operate as negative feedback elements to keep the biological variable tightly confined. We categorize known ASD-associated gene products according to their roles in such feedback loops, and provide detailed commentary for exemplar genes within each module. PMID:26985722

Using BCG as a framework for setting goals and communicating progress toward those goals

EPA Science Inventory

This 5 minute Lightning Talk will discuss the benefits of stakeholder-supported quantitative targets in measuring progress, and will describe the Biological Condition Gradient (BCG) as one way to develop these quantitative targets.

Health and Safety Research Division progress report, July 1, 1984-September 30, 1985

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

Not Available

1986-01-01

This report summarizes progress made for the period July 1984 through September 1985. Sections describe research in health studies, dosimetry and biophysical transport, biological and radiation physics, chemical physics, and risk analysis. (ACR)

Biomolecular computing systems: principles, progress and potential.

PubMed

Benenson, Yaakov

2012-06-12

The task of information processing, or computation, can be performed by natural and man-made 'devices'. Man-made computers are made from silicon chips, whereas natural 'computers', such as the brain, use cells and molecules. Computation also occurs on a much smaller scale in regulatory and signalling pathways in individual cells and even within single biomolecules. Indeed, much of what we recognize as life results from the remarkable capacity of biological building blocks to compute in highly sophisticated ways. Rational design and engineering of biological computing systems can greatly enhance our ability to study and to control biological systems. Potential applications include tissue engineering and regeneration and medical treatments. This Review introduces key concepts and discusses recent progress that has been made in biomolecular computing.

Beyond detection: biological physics informing progression and treatment of cancer Beyond detection: biological physics informing progression and treatment of cancer

NASA Astrophysics Data System (ADS)

Newman, T. J.; Thompson, A. M.

2012-12-01

The full text of the Preface is given in the PDF file. References [1] Kaur P et al 2012 Phys. Biol. 9 065001 [2] Lobikin M et al 2012 Phys. Biol. 9 065002 [3] Tanner K 2012 Phys. Biol. 9 065003 [4] Liu S V et al 2012 Phys. Biol. 9 065004 [5] Liao D et al 2012 Phys. Biol. 9 065005 [6] Liao D et al 2012 Phys. Biol. 9 065006 [7] Orlando P A et al 2012 Phys. Biol. 9 065007

Status and progress in large-scale assessment of biological diversity in the United States

Treesearch

S. R. Shifley; C. H. Flather; W. B. Smith; K. H. Riitters; C. H. Sieg

2010-01-01

Conservation of biological diversity is one of seven criteria used to evaluate forest sustainability in the United States. The status of biological diversity is characterized by nine indicators that report area, protected status, and fragmentation of forest habitats; number and conservation status of forest-associated species; range and abundance of forest species to...

SNAB: A New Advanced Level Biology Course

ERIC Educational Resources Information Center

Reiss, Michael J.

2005-01-01

Of all the sciences, biology has probably made the most rapid progress in recent years and the need for this to be reflected in a new Advanced Level biology course has long been recognised in the UK. After wide-ranging consultation and successful piloting in over 50 schools and colleges in England and Wales, the new Salters-Nuffield Advanced…

Building Capacity in Understanding Foundational Biology Concepts: A K-12 Learning Progression in Genetics Informed by Research on Children's Thinking and Learning

ERIC Educational Resources Information Center

Elmesky, Rowhea

2013-01-01

This article describes the substance, structure, and rationale of a learning progression in genetics spanning kindergarten through twelfth grade (K-12). The learning progression is designed to build a foundation towards understanding protein structure and activity and should be viewed as one possible pathway to understanding concepts of genetics…

Progression Rate Associated Peripheral Blood Biomarkers of Parkinson's Disease.

PubMed

Fan, Yanxia; Xiao, Shuping

2018-06-23

Parkinson disease (PD) is one of the most frequent neurodegenerative disorders. The aim of this study was to identify blood biomarkers capable to discriminate PD patients with different progression rates. Differentially expressed genes (DEGs) were acquired by comparing the expression profiles of PD patients with rapid and slow progression rates, using an expression dataset from Gene Expression Omnibus (GEO) under accession code of GSE80599. Altered biological processes and pathways were revealed by functional annotation. Potential biomarkers of PD were identified by protein-protein interaction (PPI) network analysis. Critical transcription factors (TFs) and miRNAs regulating DEGs were predicted by TF analysis and miRNA analysis. A total of 225 DEGs were identified between PD patients with rapid and slow progression profiles. These genes were significantly enriched in biological processes and pathways related to fatty acid metabolism. Among these DEGs, ZFAND4, SRMS, UBL4B, PVALB, DIRAS1, PDP2, LRCH1, and MYL4 were potential progression rate associated biomarkers of PD. Additionally, these DEGs may be regulated by miRNAs of the miR-30 family and TFs STAT1 and GRHL3. Our results may contribute to our understanding of the molecular mechanisms underlying different PD progression profiles.

A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression

PubMed Central

Giotopoulos, George; van der Weyden, Louise; Osaki, Hikari; Rust, Alistair G.; Gallipoli, Paolo; Meduri, Eshwar; Horton, Sarah J.; Chan, Wai-In; Foster, Donna; Prinjha, Rab K.; Pimanda, John E.; Tenen, Daniel G.; Vassiliou, George S.; Koschmieder, Steffen; Adams, David J.

2015-01-01

The introduction of highly selective ABL-tyrosine kinase inhibitors (TKIs) has revolutionized therapy for chronic myeloid leukemia (CML). However, TKIs are only efficacious in the chronic phase of the disease and effective therapies for TKI-refractory CML, or after progression to blast crisis (BC), are lacking. Whereas the chronic phase of CML is dependent on BCR-ABL, additional mutations are required for progression to BC. However, the identity of these mutations and the pathways they affect are poorly understood, hampering our ability to identify therapeutic targets and improve outcomes. Here, we describe a novel mouse model that allows identification of mechanisms of BC progression in an unbiased and tractable manner, using transposon-based insertional mutagenesis on the background of chronic phase CML. Our BC model is the first to faithfully recapitulate the phenotype, cellular and molecular biology of human CML progression. We report a heterogeneous and unique pattern of insertions identifying known and novel candidate genes and demonstrate that these pathways drive disease progression and provide potential targets for novel therapeutic strategies. Our model greatly informs the biology of CML progression and provides a potent resource for the development of candidate therapies to improve the dismal outcomes in this highly aggressive disease. PMID:26304963

Radiographic progression of large joint damage in patients with rheumatoid arthritis treated with biological disease-modifying anti-rheumatic drugs.

PubMed

Nakajima, Arata; Aoki, Yasuchika; Sonobe, Masato; Takahashi, Hiroshi; Saito, Masahiko; Terayama, Keiichiro; Nakagawa, Koichi

2016-07-01

Radiographic progression of damage to the small joints in patients with rheumatoid arthritis (RA) is well known; however, it has not been studied fully in the large joints. In this study, we looked at the prevalence of radiographic progression of large joint damage in patients with RA treated with biological disease-modifying anti-rheumatic drugs (bDMARDs). A total of 273 large joints in the upper and lower extremities of 67 patients with RA treated with bDMARDs were investigated. Radiographs for tender and/or swollen large joints were taken at least twice during the study period (mean 18.6 months), and the progression of damage was evaluated. Progressive damage was found in 20.9% of patients and 6.2% of joints. A multivariate analysis revealed that the Larsen grade (LG) alone was a risk factor for progressive damage. The LG cutoff value was determined to be 2.5 (sensitivity: 0.529, specificity: 0.805). The only factor to predict progressive damage was the LG of the joints with symptoms, and the damage must be stopped within LG II. Regular radiographic examinations for large joints should be performed in addition to routine examinations for small joints, such as the hand and foot.

Circulating Soluble Receptor Activator of Nuclear Factor Kappa B Ligand and C-C Motif Ligand 3 Correlate With Survival in Patients With Waldenström Macroglobulinemia.

PubMed

Eleutherakis-Papaiakovou, Evangelos; Kastritis, Efstathios; Gavriatopoulou, Maria; Christoulas, Dimitrios; Roussou, Maria; Ntanasis-Stathopoulos, Ioannis; Kanellias, Nikolaos; Papatheodorou, Athanasios; Dimopoulos, Meletios A; Terpos, Evangelos

2018-06-01

Serum receptor activator of nuclear factor κB ligand (sRANKL) and chemokine (C-C) motif ligand 3 (CCL-3) have been reported to be elevated in Waldenström macroglobulinemia (WM) patients. However, there are no published data regarding the prognostic value of these molecules in WM regarding progression-free and overall survival. To evaluate the effect of these markers of bone remodeling on survival parameters, we prospectively evaluated serum cytokines and biological markers in 55 patients with symptomatic WM before they received any kind of treatment. Serum levels of CCL-3 and bone remodeling markers were also evaluated in asymptomatic WM and IgM monoclonal gammopathy of undetermined significance. Furthermore, we assessed bone marrow biopsy samples from newly diagnosed WM patients for CCL-3 and RANKL expression. High circulating sRANKL values predicted shorter median overall survival (46 months vs. not reached, P = .025). High serum levels of CCL-3 predicted shorter median progression-free survival (27 months vs. not reached, P = .048). At bone marrow biopsy evaluation, the whole number of the neoplastic cells revealed strong cytoplasmic positivity for CCL-3, while the neoplastic clone did not express RANKL. We conclude that WM cells produce CCL-3 and possibly enhance the production of RANKL in the bone microenvironment. The correlation of sRANKL and CCL-3 with survival reveals the importance of these cytokines in disease biology and highlights the significance of the interactions between WM and stromal cells for the development of WM. Finally, these findings provide the rationale for the use of anti-RANKL and anti-CCL-3 drugs in animal models of WM before their clinical evaluation. Copyright © 2018 Elsevier Inc. All rights reserved.

The retinal specific CD147 Ig0 domain: from molecular structure to biological activity

PubMed Central

Redzic, Jasmina S.; Armstrong, Geoffrey S.; Isern, Nancy. G.; Jones, David N.M.; Kieft, Jeffrey S.; Eisenmesser, Elan Zohar

2011-01-01

CD147 is a type I transmembrane protein that is involved in inflammatory diseases, cancer progression, and multiple human pathogens utilize CD147 for efficient infection. In several cancers, CD147 expression is so high that it is now used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified, differing in their number of immunoglobulin (Ig)-like domains. These include CD147 Ig1-Ig2 that is ubiquitously expressed in most tissues and CD147 Ig0-Ig1-Ig2 that is retinal specific and implicated in retinoblastoma. However, little is known in regard to the retinal specific CD147 Ig0 domain despite its potential role in retinoblastoma. We present the first crystal structure of the human CD147 Ig0 domain and show that the CD147 Ig0 domain is a crystallographic dimer with an I-type domain structure, which is maintained in solution. Furthermore, we have utilized our structural data together with mutagenesis to probe the biological activity of CD147-containing proteins both with and without the CD147 Ig0 domain within several model cell lines. Our findings reveal that the CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 domain has its own receptor distinct from that of the other CD147 Ig-like domains, CD147 Ig1-Ig2. Finally, we show that the CD147 Ig0 dimer is the functional unit required for activity and can be disrupted by a single point mutation. PMID:21620857

Expression of breast cancer metastasis suppressor-1, BRMS-1, in human breast cancer and the biological impact of BRMS-1 on the migration of breast cancer cells.

PubMed

Zhang, Yulu; Ye, Lin; Tan, Yuxia; Sun, Pinghui; Ji, Ke; Jiang, Wen G

2014-03-01

Breast cancer metastasis suppressor-1 (BRMS1) is a candidate metastasis-suppressing gene and has been shown to potentially inhibit tumor progression without blocking the growth of orthotopic tumors, in different tumor types including non-small cell lung cancer, ovarian, melanoma and breast cancers. BRMS-1 gene transcript was quantified in breast cancer sample tissues and analyzed against histological and clinical patient outcome. Human breast cancer cell lines, MDA MB-231 and MCF-7 were used to genetically-modify the expression of BRMS-1 and test for biological responses following BRMS-1 modifications. Key candidate signal pathways, influenced by BRMS-1 were also explored. BRMS1 was present in MDA MB-231 and MCF-7 cell lines. Using anti-BRMS1 transgenes, we knocked-down the transcripts of BRMS1 in both cells at the mRNA and protein levels. Knockdown of BRMS1 gave both cells a faster cell growth rate, rapid pace of cellular migration and invasion, compared to respective wild-type and control cells (p<0.05). Blocking phospholipase-Cγ (PLCγ) had a significant influence on the BRMS-1-induced cell migration. Finally, significantly low levels of BRMS1 were observed in patients with high-grade tumors (p=0.12), in patients with distant metastasis (p=0.05) and those who died of breast cancer (p=0.0037). In addition, patients with low levels of BRMS1 had a significantly shorter overall survival (p=0.035). BRMS-1 is aberrantly expressed in human breast cancer and is inversely-correlated with disease progression and patient survival. This is likely to be occurring via its influence on invasion and migration of breast cancer cells.

Progression of trunk imbalance in adolescent idiopathic scoliosis with a thoracolumbar/lumbar curve: is it predictable at the initial visit?

PubMed

Hwang, Chang Ju; Lee, Choon Sung; Lee, Dong-Ho; Cho, Jae Hwan

2017-11-01

OBJECTIVE Progression of trunk imbalance is an important finding during follow-up of patients with adolescent idiopathic scoliosis (AIS). Nevertheless, no factors that predict progression of trunk imbalance have been identified. The purpose of this study was to identify parameters that predict progression of trunk imbalance in cases of AIS with a structural thoracolumbar/lumbar (TL/L) curve. METHODS This study included 105 patients with AIS and a structural TL/L curve who were followed up at an outpatient clinic. Patients with trunk imbalance (trunk shift ≥ 20 mm) at the initial visit were excluded. All patients were followed up for more than 2 years. Patients were divided into the following groups according to progression of trunk imbalance: 1) Group P, trunk shift ≥ 20 mm at the final visit and degree of progression ≥ 10 mm; and 2) Group NP, trunk shift < 20 mm at the final visit or degree of progression < 10 mm. Radiological parameters included Cobb angle, upper end vertebrae and lower end vertebrae (LEV), LEV tilt, disc wedge angle between LEV and LEV+1, trunk shift, apical vertebral translation, and apical vertebral rotation (AVR). Each parameter was compared between groups. Radiological parameters were assessed at every visit using whole-spine standing anteroposterior radiographs. RESULTS Among the 105 patients examined, 13 showed trunk imbalance with progression ≥ 10 mm at the final visit (Group P). Multivariate logistic regression analysis identified a lower Risser grade (p = 0.002) and a greater initial AVR (p = 0.020) as predictors of progressive trunk imbalance. A change in LEV tilt during follow-up was associated with trunk imbalance (p = 0.001). CONCLUSIONS Risser grade and AVR measured at the initial visit may predict progression of trunk imbalance. Surgeons should consider the risk of progressive trunk imbalance if patients show skeletal immaturity and a greater AVR at the initial visit.

Final Technical Progress Report: Development of Low-Cost Suspension Heliostat; December 7, 2011 - December 6, 2012

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

Bender, W.

2013-01-01

Final technical progress report of SunShot Incubator Solaflect Energy. The project succeeded in demonstrating that the Solaflect Suspension Heliostat design is viable for large-scale CSP installations. Canting accuracy is acceptable and is continually improving as Solaflect improves its understanding of this design. Cost reduction initiatives were successful, and there are still many opportunities for further development and further cost reduction.

On nonepistemic values in conservation biology.

PubMed

Baumgaertner, Bert; Holthuijzen, Wieteke

2017-02-01

Conservation biology is a uniquely interdisciplinary science with strong roots in ecology, but it also embraces a value-laden and mission-oriented framework. This combination of science and values causes conservation biology to be at the center of critique regarding the discipline's scientific credibility-especially the division between the realms of theory and practice. We identify this dichotomy between seemingly objective (fact-based) and subjective (value-laden) practices as the measure-value dichotomy, whereby measure refers to methods and analyses used in conservation biology (i.e., measuring biodiversity) and value refers to nonepistemic values. We reviewed and evaluated several landmark articles central to the foundation of conservation biology and concepts of biodiversity with respect to their attempts to separate measures and values. We argue that the measure-value dichotomy is false and that conservation biology can make progress in ways unavailable to other disciplines because its practitioners are tasked with engaging in both the realm of theory and the realm of practice. The entanglement of measures and values is by no means a weakness of conservation biology. Because central concepts such as biodiversity contain both factual and evaluative aspects, conservation biologists can make theoretical progress by examining, reviewing, and forming the values that are an integral part of those concepts. We suggest that values should be included and analyzed with respect to the methods, results, and conclusions of scientific work in conservation biology. © 2016 Society for Conservation Biology.

COX-derived prostanoid pathways in gastrointestinal cancer development and progression: novel targets for prevention and intervention.

PubMed

Cathcart, Mary-Clare; O'Byrne, Kenneth J; Reynolds, John V; O'Sullivan, Jacintha; Pidgeon, Graham P

2012-01-01

Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies. COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers were significantly reduced by daily aspirin intake. A number of randomized controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors. However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk. More recently, downstream effectors of COX-signaling have been investigated in cancer development/progression. PGE(2), which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA(2) in G.I. cancers has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD(2) and its metabolite 15d-PGJ2, PGF(1α) and PGI(2). Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity. A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will also be discussed. Finally, we will highlight the latest pre-clinical technologies as well as avenues for future investigation in this highly topical research field. Copyright © 2011 Elsevier B.V. All rights reserved.

Engineering Lubrication in Articular Cartilage

PubMed Central

McNary, Sean M.; Athanasiou, Kyriacos A.

2012-01-01

Despite continuous progress toward tissue engineering of functional articular cartilage, significant challenges still remain. Advances in morphogens, stem cells, and scaffolds have resulted in enhancement of the bulk mechanical properties of engineered constructs, but little attention has been paid to the surface mechanical properties. In the near future, engineered tissues will be able to withstand and support the physiological compressive and tensile forces in weight-bearing synovial joints such as the knee. However, there is an increasing realization that these tissue-engineered cartilage constructs will fail without the optimal frictional and wear properties present in native articular cartilage. These characteristics are critical to smooth, pain-free joint articulation and a long-lasting, durable cartilage surface. To achieve optimal tribological properties, engineered cartilage therapies will need to incorporate approaches and methods for functional lubrication. Steady progress in cartilage lubrication in native tissues has pushed the pendulum and warranted a shift in the articular cartilage tissue-engineering paradigm. Engineered tissues should be designed and developed to possess both tribological and mechanical properties mirroring natural cartilage. In this article, an overview of the biology and engineering of articular cartilage structure and cartilage lubrication will be presented. Salient progress in lubrication treatments such as tribosupplementation, pharmacological, and cell-based therapies will be covered. Finally, frictional assays such as the pin-on-disk tribometer will be addressed. Knowledge related to the elements of cartilage lubrication has progressed and, thus, an opportune moment is provided to leverage these advances at a critical step in the development of mechanically and tribologically robust, biomimetic tissue-engineered cartilage. This article is intended to serve as the first stepping stone toward future studies in functional tissue engineering of articular cartilage that begins to explore and incorporate methods of lubrication. PMID:21955119

Current progress in tissue engineering of heart valves: multiscale problems, multiscale solutions.

PubMed

Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T

2015-01-01

Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Whereas much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells.

Current Progress in Tissue Engineering of Heart Valves: Multiscale Problems, Multiscale Solutions

PubMed Central

Cheung, Daniel Y; Duan, Bin; Butcher, Jonathan T.

2016-01-01

Introduction Heart valve disease is an increasingly prevalent and clinically serious condition. There are no clinically effective biological diagnostics or treatment strategies. The only recourse available is replacement with a prosthetic valve, but the inability of these devices to grow or respond biologically to their environments necessitates multiple resizing surgeries and life-long coagulation treatment, especially in children. Tissue engineering has a unique opportunity to impact heart valve disease by providing a living valve conduit, capable of growth and biological integration. Areas covered This review will cover current tissue engineering strategies in fabricating heart valves and their progress towards the clinic, including molded scaffolds using naturally-derived or synthetic polymers, decellularization, electrospinning, 3D bioprinting, hybrid techniques, and in vivo engineering. Expert opinion While much progress has been made to create functional living heart valves, a clinically viable product is not yet realized. The next leap in engineered living heart valves will require a deeper understanding of how the natural multi-scale structural and biological heterogeneity of the tissue ensures its efficient function. Related, improved fabrication strategies must be developed that can replicate this de novo complexity, which is likely instructive for appropriate cell differentiation and remodeling whether seeded with autologous stem cells in vitro or endogenously recruited cells. PMID:26027436

Healthy aging and disease: role for telomere biology?

PubMed Central

Zhu, Haidong; Belcher, Matthew; van der Harst, Pim

2011-01-01

Aging is a biological process that affects most cells, organisms and species. Human aging is associated with increased susceptibility to a variety of chronic diseases, including cardiovascular disease, Type 2 diabetes, neurological diseases and cancer. Despite the remarkable progress made during the last two decades, our understanding of the biology of aging remains incomplete. Telomere biology has recently emerged as an important player in the aging and disease process. PMID:21271986

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

Systems Biology-an interdisciplinary approach.

PubMed

Friboulet, Alain; Thomas, Daniel

2005-06-15

System-level approaches in biology are not new but foundations of "Systems Biology" are achieved only now at the beginning of the 21st century [Kitano, H., 2001. Foundations of Systems Biology. MIT Press, Cambridge, MA]. The renewed interest for a system-level approach is linked to the progress in collecting experimental data and to the limits of the "reductionist" approach. System-level understanding of native biological and pathological systems is needed to provide potential therapeutic targets. Examples of interdisciplinary approach in Systems Biology are described in U.S., Japan and Europe. Robustness in biology, metabolic engineering and idiotypic networks are discussed in the framework of Systems Biology.

NIH Research: Cancers: A "Constellation" of Diseases | NIH MedlinePlus the Magazine

MedlinePlus

... Dr. Varmus received early training in genetics and molecular biology at the National Cancer Institute (NCI) in the ... now new technologies for genomic analysis. Progress in molecular biology has transformed our ability to understand the broken ...

Quality of Life and Anxiety in Younger Patients after Biological versus Mechanical Aortic Valve Replacement.

PubMed

Kottmaier, Marc; Hettich, Ina; Deutsch, Marcus-André; Badiu, Catalin; Krane, Markus; Lange, Ruediger; Bleiziffer, Sabine

2017-04-01

Background  Since biological valve recipients are likely to need a redo procedure in the future for valve deterioration, we hypothesized patients might be more fearful about the progression of their disease than patients after aortic valve replacement (AVR) with a mechanical valve. The aim of this study is to compare the quality of life (QOL) and anxiety in patients who have undergone biological versus mechanical AVR. Method  A total of 56 patients after mechanical AVR (mean age: 64.4 ± 8.17 years) and 66 patients after biological AVR (mean age: 64.8 ± 11.05 years) received three questionnaires 5.66 (± 2.68) years after surgery, including: The short form-36 (SF-36) to assess QOL, the fear of progression questionnaire (FOP), and the cardiac anxiety questionnaire (CAQ) to assess general anxiety, anxiety related to cardiac symptoms, and anxiety about progression of heart disease and valve and anticoagulation-specific questions. Results  No significant differences were found for all categories of the SF-36. The FOP showed significantly favorable values for the biological AVR group. The CAQ showed a tendency in the subscale "avoidance" (i.e., avoidance of pulse increase) and "attention" towards more favorable values for the biological AVR group. Conclusions  In contrast to our hypothesis, patients after mechanical AVR show significantly higher anxiety values for the FOP, and a tendency toward higher values for "avoidance" (i.e., avoidance of pulse increase). Partnership concerns, especially in terms of sexuality can be explained by factors that are recognizable for the partner, such as valve sound. These data provide evidence that factors that are continuously present after mechanical AVR, such as valve sound or anticoagulation might affect wellbeing stronger than the certainty of reoperation in the future after biological AVR. We conclude that implantation of a biological prosthesis can be justified in younger patients with regards to QOL. Georg Thieme Verlag KG Stuttgart · New York.

Causal Assessment of Biological Impairment in the Bogue Homo River, Mississippi Using the U.S. EPA’s Stressor Identification Methodology (Final)

EPA Science Inventory

EPA announced the availability of the final report, Causal Assessment of Biological Impairment in the Bogue Homo River, Mississippi Using the U.S. EPA’s Stressor Identification Methodology. This assessment is taken from more than 700 court ordered assessments of the cau...

Creating a dashboard to track progress toward IOM recommendations for the future of nursing.

PubMed

Spetz, Joanne; Bates, Timothy; Chu, Lela; Lin, Jessica; Fishman, Nancy W; Melichar, Lori

2013-01-01

This article explains the process used to identify and develop a set of data used to track national progress toward the recommendations of the Institute of Medicine Committee for the Future of Nursing. The data are presented in a dashboard format to visually summarize information and quickly measure progress. The approach selected by the research team is outlined, the criteria for selecting candidate metrics are detailed, the process for seeking external guidance is described, and the final dashboard measures are presented. Finally, the methods for data collection for each metric are explicated, to guide states and local regions in the collection of their own data.

Exosomes and Homeostatic Synaptic Plasticity Are Linked to Each other and to Huntington's, Parkinson's, and Other Neurodegenerative Diseases by Database-Enabled Analyses of Comprehensively Curated Datasets

PubMed Central

Wang, James K. T.; Langfelder, Peter; Horvath, Steve; Palazzolo, Michael J.

2017-01-01

Huntington's disease (HD) is a progressive and autosomal dominant neurodegeneration caused by CAG expansion in the huntingtin gene (HTT), but the pathophysiological mechanism of mutant HTT (mHTT) remains unclear. To study HD using systems biological methodologies on all published data, we undertook the first comprehensive curation of two key PubMed HD datasets: perturbation genes that impact mHTT-driven endpoints and therefore are putatively linked causally to pathogenic mechanisms, and the protein interactome of HTT that reflects its biology. We perused PubMed articles containing co-citation of gene IDs and MeSH terms of interest to generate mechanistic gene sets for iterative enrichment analyses and rank ordering. The HD Perturbation database of 1,218 genes highly overlaps the HTT Interactome of 1,619 genes, suggesting links between normal HTT biology and mHTT pathology. These two HD datasets are enriched for protein networks of key genes underlying two mechanisms not previously implicated in HD nor in each other: exosome synaptic functions and homeostatic synaptic plasticity. Moreover, proteins, possibly including HTT, and miRNA detected in exosomes from a wide variety of sources also highly overlap the HD datasets, suggesting both mechanistic and biomarker links. Finally, the HTT Interactome highly intersects protein networks of pathogenic genes underlying Parkinson's, Alzheimer's and eight non-HD polyglutamine diseases, ALS, and spinal muscular atrophy. These protein networks in turn highly overlap the exosome and homeostatic synaptic plasticity gene sets. Thus, we hypothesize that HTT and other neurodegeneration pathogenic genes form a large interlocking protein network involved in exosome and homeostatic synaptic functions, particularly where the two mechanisms intersect. Mutant pathogenic proteins cause dysfunctions at distinct points in this network, each altering the two mechanisms in specific fashion that contributes to distinct disease pathologies, depending on the gene mutation and the cellular and biological context. This protein network is rich with drug targets, and exosomes may provide disease biomarkers, thus enabling drug discovery. All the curated datasets are made available for other investigators. Elucidating the roles of pathogenic neurodegeneration genes in exosome and homeostatic synaptic functions may provide a unifying framework for the age-dependent, progressive and tissue selective nature of multiple neurodegenerative diseases. PMID:28611571

Exosomes and Homeostatic Synaptic Plasticity Are Linked to Each other and to Huntington's, Parkinson's, and Other Neurodegenerative Diseases by Database-Enabled Analyses of Comprehensively Curated Datasets.

PubMed

Wang, James K T; Langfelder, Peter; Horvath, Steve; Palazzolo, Michael J

2017-01-01

Huntington's disease (HD) is a progressive and autosomal dominant neurodegeneration caused by CAG expansion in the huntingtin gene ( HTT ), but the pathophysiological mechanism of mutant HTT (mHTT) remains unclear. To study HD using systems biological methodologies on all published data, we undertook the first comprehensive curation of two key PubMed HD datasets: perturbation genes that impact mHTT-driven endpoints and therefore are putatively linked causally to pathogenic mechanisms, and the protein interactome of HTT that reflects its biology. We perused PubMed articles containing co-citation of gene IDs and MeSH terms of interest to generate mechanistic gene sets for iterative enrichment analyses and rank ordering. The HD Perturbation database of 1,218 genes highly overlaps the HTT Interactome of 1,619 genes, suggesting links between normal HTT biology and mHTT pathology. These two HD datasets are enriched for protein networks of key genes underlying two mechanisms not previously implicated in HD nor in each other: exosome synaptic functions and homeostatic synaptic plasticity. Moreover, proteins, possibly including HTT, and miRNA detected in exosomes from a wide variety of sources also highly overlap the HD datasets, suggesting both mechanistic and biomarker links. Finally, the HTT Interactome highly intersects protein networks of pathogenic genes underlying Parkinson's, Alzheimer's and eight non-HD polyglutamine diseases, ALS, and spinal muscular atrophy. These protein networks in turn highly overlap the exosome and homeostatic synaptic plasticity gene sets. Thus, we hypothesize that HTT and other neurodegeneration pathogenic genes form a large interlocking protein network involved in exosome and homeostatic synaptic functions, particularly where the two mechanisms intersect. Mutant pathogenic proteins cause dysfunctions at distinct points in this network, each altering the two mechanisms in specific fashion that contributes to distinct disease pathologies, depending on the gene mutation and the cellular and biological context. This protein network is rich with drug targets, and exosomes may provide disease biomarkers, thus enabling drug discovery. All the curated datasets are made available for other investigators. Elucidating the roles of pathogenic neurodegeneration genes in exosome and homeostatic synaptic functions may provide a unifying framework for the age-dependent, progressive and tissue selective nature of multiple neurodegenerative diseases.

Biology Division progress report for period of October 1, 1988--September 30, 1989

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

Not Available

1990-02-01

The Biology Division of the Oak Ridge National Laboratory is one component of the Department of Energy's intramural program in life sciences. With respect to experimental biology, the congressionally mandated mission of this Office is to study adverse health effects of energy production and utilization. Within this stated broad mission, common themes among the research programs of the Biology Division are interactions of animals, cells, and molecules with their respective environments. Investigations focus on genetic and somatic effects of radiation and chemicals. Goals include identification and quantification of these effects, elucidation of pathways by which the effects are expressed, assessmentmore » of risks associated with radiation and chemical exposures, and establishment of strategies for extrapolation of risk data from animals to humans. Concurrent basic studies in genetics, biochemistry, molecular biology, and cell biology illuminate normal life processes as prerequisites to comprehending mutagenic and carcinogenic effects of environmental agents. This Progress Report is intended to provide both broad perspectives of the Division's research programs and synopses of recent achievements. Readers are invited to contact individual principal investigators for more detailed information, including reprints of publications. 120 refs.« less

Multiagent cooperation and competition with deep reinforcement learning.

PubMed

Tampuu, Ardi; Matiisen, Tambet; Kodelja, Dorian; Kuzovkin, Ilya; Korjus, Kristjan; Aru, Juhan; Aru, Jaan; Vicente, Raul

2017-01-01

Evolution of cooperation and competition can appear when multiple adaptive agents share a biological, social, or technological niche. In the present work we study how cooperation and competition emerge between autonomous agents that learn by reinforcement while using only their raw visual input as the state representation. In particular, we extend the Deep Q-Learning framework to multiagent environments to investigate the interaction between two learning agents in the well-known video game Pong. By manipulating the classical rewarding scheme of Pong we show how competitive and collaborative behaviors emerge. We also describe the progression from competitive to collaborative behavior when the incentive to cooperate is increased. Finally we show how learning by playing against another adaptive agent, instead of against a hard-wired algorithm, results in more robust strategies. The present work shows that Deep Q-Networks can become a useful tool for studying decentralized learning of multiagent systems coping with high-dimensional environments.

Microbial Routes to (2R,3R)-2,3-Butanediol: Recent Advances and Future Prospects.

PubMed

Xie, Neng-Zhong; Chen, Xian-Rui; Wang, Qing-Yan; Chen, Dong; Du, Qi-Shi; Zhou, Guo-Ping; Huang, Ri-Bo

2017-01-01

(2R,3R)-2,3-Butanediol has many industrial applications, such as it is used as an antifreeze agent and low freezing point fuel. In addition, it is particularly important to provide chiral groups in drugs. In recent years, this valuable bio-based chemical has attracted increasing attention, and significant progress has been made in the development of microbial cell factories for (2R,3R)-2,3-butanediol production. This article reviews recent advances and challenges in microbial routes to (2R,3R)-2,3- butanediol production, and highlights the metabolic engineering and synthetic biological approaches used to improve titers, yields, productivities, and optical purities. Finally, a systematic and integrative strategy for developing high-performance microbial cell factories is proposed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

How to make spinal motor neurons.

PubMed

Davis-Dusenbery, Brandi N; Williams, Luis A; Klim, Joseph R; Eggan, Kevin

2014-02-01

All muscle movements, including breathing, walking, and fine motor skills rely on the function of the spinal motor neuron to transmit signals from the brain to individual muscle groups. Loss of spinal motor neuron function underlies several neurological disorders for which treatment has been hampered by the inability to obtain sufficient quantities of primary motor neurons to perform mechanistic studies or drug screens. Progress towards overcoming this challenge has been achieved through the synthesis of developmental biology paradigms and advances in stem cell and reprogramming technology, which allow the production of motor neurons in vitro. In this Primer, we discuss how the logic of spinal motor neuron development has been applied to allow generation of motor neurons either from pluripotent stem cells by directed differentiation and transcriptional programming, or from somatic cells by direct lineage conversion. Finally, we discuss methods to evaluate the molecular and functional properties of motor neurons generated through each of these techniques.

Label-Free Molecular Imaging of Biological Cells and Tissues by Linear and Nonlinear Raman Spectroscopic Approaches.

PubMed

Krafft, Christoph; Schmitt, Michael; Schie, Iwan W; Cialla-May, Dana; Matthäus, Christian; Bocklitz, Thomas; Popp, Jürgen

2017-04-10

Raman spectroscopy is an emerging technique in bioanalysis and imaging of biomaterials owing to its unique capability of generating spectroscopic fingerprints. Imaging cells and tissues by Raman microspectroscopy represents a nondestructive and label-free approach. All components of cells or tissues contribute to the Raman signals, giving rise to complex spectral signatures. Resonance Raman scattering and surface-enhanced Raman scattering can be used to enhance the signals and reduce the spectral complexity. Raman-active labels can be introduced to increase specificity and multimodality. In addition, nonlinear coherent Raman scattering methods offer higher sensitivities, which enable the rapid imaging of larger sampling areas. Finally, fiber-based imaging techniques pave the way towards in vivo applications of Raman spectroscopy. This Review summarizes the basic principles behind medical Raman imaging and its progress since 2012. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bioinformatics and molecular modeling in glycobiology

PubMed Central

Schloissnig, Siegfried

2010-01-01

The field of glycobiology is concerned with the study of the structure, properties, and biological functions of the family of biomolecules called carbohydrates. Bioinformatics for glycobiology is a particularly challenging field, because carbohydrates exhibit a high structural diversity and their chains are often branched. Significant improvements in experimental analytical methods over recent years have led to a tremendous increase in the amount of carbohydrate structure data generated. Consequently, the availability of databases and tools to store, retrieve and analyze these data in an efficient way is of fundamental importance to progress in glycobiology. In this review, the various graphical representations and sequence formats of carbohydrates are introduced, and an overview of newly developed databases, the latest developments in sequence alignment and data mining, and tools to support experimental glycan analysis are presented. Finally, the field of structural glycoinformatics and molecular modeling of carbohydrates, glycoproteins, and protein–carbohydrate interaction are reviewed. PMID:20364395

Multipurpose Wetlands Phase II/III: final design and ongoing research investigations

USGS Publications Warehouse

Babbitt, Bruce; Beard, Daniel P.; Hancock, Lawrence F.

1994-01-01

The Eastern Municipal Water District (EMWD), the Bureau of Reclamation (USBR), and the National Biological Survey (NBS), in consultation with other governmental agencies, the academic community, and environmental groups, are involved in a cooperative wetlands research and demonstration effort. This report reflects progress through the first 3 years of a 5-year program. The goal of the Multipurpose Wetlands Research and Demonstration Project is to evaluate and expand the use of reclaimed water and contaminated ground water through the incorporation of multipurpose constructed wetlands into EMWD's total water resources management program. The focus of the wetlands is the development of design, construction, and operation criteria that will provide a cost-effective and innovative alternative for managing water resources and provide other public benefits in arid areas. The program also recognizes the fact that naturally-occurring wetlands, both coastal and inland, have been disappearing at an alarming rate.

Luminescence materials for pH and oxygen sensing in microbial cells - structures, optical properties, and biological applications.

PubMed

Zou, Xianshao; Pan, Tingting; Chen, Lei; Tian, Yanqing; Zhang, Weiwen

2017-09-01

Luminescence including fluorescence and phosphorescence sensors have been demonstrated to be important for studying cell metabolism, and diagnosing diseases and cancer. Various design principles have been employed for the development of sensors in different formats, such as organic molecules, polymers, polymeric hydrogels, and nanoparticles. The integration of the sensing with fluorescence imaging provides valuable tools for biomedical research and applications at not only bulk-cell level but also at single-cell level. In this article, we critically reviewed recent progresses on pH, oxygen, and dual pH and oxygen sensors specifically for their application in microbial cells. In addition, we focused not only on sensor materials with different chemical structures, but also on design and applications of sensors for better understanding cellular metabolism of microbial cells. Finally, we also provided an outlook for future materials design and key challenges in reaching broad applications in microbial cells.

SERI Biomass Program

NASA Astrophysics Data System (ADS)

Bergeron, P. W.; Corder, R. E.; Hill, A. M.; Lindsey, H.; Lowenstein, M. Z.

1983-02-01

The biomass with which this report is concerned includes aquatic plants, which can be converted into liquid fuels and chemicals; organic wastes (crop residues as well as animal and municipal wastes), from which biogas can be produced via anerobic digestion; and organic or inorganic waste streams, from which hydrogen can be produced by photobiological processes. The Biomass Program Office supports research in three areas which, although distinct, all use living organisms to create the desired products. The Aquatic Species Program (ASP) supports research on organisms that are themselves processed into the final products, while the Anaerobic Digestion (ADP) and Photo/Biological Hydrogen Program (P/BHP) deals with organisms that transform waste streams into energy products. The P/BHP is also investigating systems using water as a feedstock and cell-free systems which do not utilize living organisms. This report summarizes the progress and research accomplishments of the SERI Biomass Program during FY 1982.

Summary of a symposium on natriuretic and digitalis-like factors.

PubMed

Buckalew, V M; Gonick, H C

1998-01-01

An international symposium on natriuretic and digitalis-like factors was convened for the first time since 1992. Topics discussed included structures and biosynthesis of endogenous digitalis-like factors (EDLF), biologic activities, physiology function and role of EDLF in hypertension, and novel natriuretic factors. Progress was reported in determining the exact structure of an isomer of ouabain isolated from bovine hypothalamus. Evidence was presented supporting the existence of a second mammalian EDLF that resembles steroids found in toads (bufodienolides). Support for endogenous synthesis of mammalian EDLF was also presented. Mammalian EDLF were reported to have effects which are different from those possessed by digitalis like steroids derived from plants. New evidence was presented implicating EDLF in various forms of hypertension in humans and animal models. Finally, several unique natriuretic factors that do not inhibit Na, K ATPase and that appear to play a role in mammalian volume regulation were discussed.

2001 Gordon Research Conference on Archaea: Ecology [sic], Metabolism. Final progress report [agenda and attendee list

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

Daniels, Charles

2001-08-10

The Gordon Research Conference on Archaea: Ecology, Metabolism [and Molecular Biology] was held at Proctor Academy, Andover, New Hampshire, August 5-10, 2001. The conference was attended by 135 participants. The attendees represented the spectrum of endeavor in this field, coming from academia, industry, and government laboratories, and included US and foreign scientists, senior researchers, young investigators, and students. Emphasis was placed on current unpublished research and discussion of the future target areas in this field. There was a conscious effort to stimulate discussion about the key issues in the field today. Session topics included the following: Ecology and genetic elements;more » Genomics and evolution; Ecology, genomes and gene regulation; Replication and recombination; Chromatin and transcription; Gene regulation; Post-transcription processing; Biochemistry and metabolism; Proteomics and protein structure; Metabolism and physiology. The featured speaker addressed the topic: ''Archaeal viruses, witnesses of prebiotic evolution?''« less

Mass Spectrometry Analyses of Multicellular Tumor Spheroids.

PubMed

Acland, Mitchell; Mittal, Parul; Lokman, Noor A; Klingler-Hoffmann, Manuela; Oehler, Martin K; Hoffmann, Peter

2018-05-01

Multicellular tumor spheroids (MCTS) are a powerful biological in vitro model, which closely mimics the 3D structure of primary avascularized tumors. Mass spectrometry (MS) has established itself as a powerful analytical tool, not only to better understand and describe the complex structure of MCTS, but also to monitor their response to cancer therapeutics. The first part of this review focuses on traditional mass spectrometry approaches with an emphasis on elucidating the molecular characteristics of these structures. Then the mass spectrometry imaging (MSI) approaches used to obtain spatially defined information from MCTS is described. Finally the analysis of primary spheroids, such as those present in ovarian cancer, and the great potential that mass spectrometry analysis of these structures has for improved understanding of cancer progression and for personalized in vitro therapeutic testing is discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fifth Annual Report: 2008 Pre-Construction Eelgrass Monitoring and Propagation for King County Outfall Mitigation

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

Woodruff, Dana L.; Judd, Chaeli; Thom, Ronald M.

2010-01-01

This is the fifth and final report in a series documenting progress of the pre-construction eelgrass restoration and mitigation activities for the proposed King County Brightwater marine outfall, discharging to Puget Sound near Point Wells, Washington. King County began implementing a multiyear eelgrass monitoring and restoration program in 2004, with the primary goal of returning intertidal and shallow subtidal habitat and eelgrass to pre-construction conditions, after construction of the outfall. Major eelgrass mitigation program elements include: a) pre-construction monitoring, i.e., documenting initial eelgrass conditions and degree of fluctuation over a 5 year period prior to construction, b) eelgrass transplanting, includingmore » harvesting, offsite propagation and stockpiling of local plants for post-construction planting, and c) post-construction planting and subsequent monitoring, occurring in 2009 and beyond. The overall program is detailed in the Eelgrass Restoration and Biological Resources Implementation Workplan (King County 2008).« less

[Synthesis and regulation of flavor compounds derived from brewing yeast: Esters].

PubMed

Loviso, Claudia L; Libkind, Diego

2018-04-04

During brewing process yeast produce more than 500 chemical compounds that can negatively and positively impact beer at the organoleptic level. In recent years, and particularly thanks to the advancement of molecular biology and genomics, there has been considerable progress in our understanding about the molecular and cellular basis of the synthesis and regulation of many of these flavor compounds. This article focuses on esters, responsible for the floral and fruity beer flavor. Its formation depends on various enzymes and factors such as the concentration of wort nutrients, the amount of dissolved oxygen and carbon dioxide, fermentation temperature and mainly the genetics of the yeast used. We provide information about how the esters originate and how is the impact of different fermentative parameters on the final concentrations of these compounds and the quality of the end product. Copyright © 2018 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.

Wildlife habitat management on the northern prairie landscape

USGS Publications Warehouse

Johnson, Douglas H.; Haseltine, Susan D.; Cowardin, Lewis M.

1994-01-01

The northern prairie landscape has changed dramatically within the past century as a result of settlement by Europeans. Natural ecosystems have been disrupted and wildlife populations greatly altered. Natural resource agencies control only limited areas within the landscape, which they cannot manage independently of privately owned lands. Wildlife managers need first to set quantifiable objectives, based on the survival, reproduction, and distribution of wildlife. Second, they need to build public support and partnerships for meeting those objectives. Finally, they need to evaluate progress not only with respect to attitudes of the public and partners but, more importantly, of the wildlife response. This paper describes some useful tools for managing information at all phases of this process. We follow by discussing management options at a landscape level. Examples are given that involve agency lands as well as private lands, managed for biological resources and diversity as well as economic sustainability.

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

Yu, Fujun; Zheng, Jianjian; Mao, Yuqing

In this study, we aimed at assessing a role of Alu-mediated p21 transcriptional regulator (APTR) in hepatofibrogenesis. APTR was upregulated in fibrotic liver samples and activated hepatic stellate cells (HSCs). Knockdown of APTR inhibited the activation of HSCs in vitro and mitigated the accumulation of collagen in vivo. Importantly, APTR silencing could abrogate TGF-β{sub 1}-induced upregulation of α-SMA in HSCs. In addition, inhibition of cell cycle and cell proliferation by APTR knockdown was attenuated by p21 siRNA1 in primary HSCs. Finally, serum APTR levels were increased in patients with liver cirrhosis, indicating a potential biomarker for liver cirrhosis. Collectively, evidence is proposedmore » for a new biological role of APTR in hepatofibrogenesis. - Highlights: • APTR is upregulated in fibrotic liver tissues and activated HSCs. • APTR silencing inhibits HSC activation and the progression of liver fibrosis. • Antifibrotic effect of APTR silencing is achieved by increasing p21.« less

GPCRs: What Can We Learn from Molecular Dynamics Simulations?

PubMed

Velgy, Naushad; Hedger, George; Biggin, Philip C

2018-01-01

Advances in the structural biology of G-protein Coupled Receptors have resulted in a significant step forward in our understanding of how this important class of drug targets function at the molecular level. However, it has also become apparent that they are very dynamic molecules, and moreover, that the underlying dynamics is crucial in shaping the response to different ligands. Molecular dynamics simulations can provide unique insight into the dynamic properties of GPCRs in a way that is complementary to many experimental approaches. In this chapter, we describe progress in three distinct areas that are particularly difficult to study with other techniques: atomic level investigation of the conformational changes that occur when moving between the various states that GPCRs can exist in, the pathways that ligands adopt during binding/unbinding events and finally, the influence of lipids on the conformational dynamics of GPCRs.

Current considerations regarding food addiction.

PubMed

Schulte, Erica M; Joyner, Michelle A; Potenza, Marc N; Grilo, Carlos M; Gearhardt, Ashley N

2015-04-01

"Food addiction" is an emerging area, and behavioral and biological overlaps have been observed between eating and addictive disorders. Potential misconceptions about applying an addiction framework to problematic eating behavior may inhibit scientific progress. Critiques of "food addiction" that focus on descriptive differences between overeating and illicit drugs are similar to early criticisms of the addictiveness of tobacco. Although food is necessary for survival, the highly processed foods associated with addictive-like eating may provide little health benefit. Individual differences are important in determining who develops an addiction. If certain foods are addictive, the identification of possible risk factors for "food addiction" is an important next step. Not all treatments for addiction require abstinence. Addiction interventions that focus on moderation or controlled use may lead to novel approaches to treating eating-related problems. Finally, addiction-related policies that focus on environmental (instead of educational) targets may have a larger public health impact in reducing overeating.

Synthesis and Biomedical Applications of Poly((meth)acrylic acid) Brushes.

PubMed

Qu, Zhenyuan; Xu, Hong; Gu, Hongchen

2015-07-15

Poly((meth)acrylic acid) (P(M)AA) brushes possess a number of distinctive properties that are particularly attractive for biomedical applications. This minireview summarizes recent advances in the synthesis and biomedical applications of P(M)AA brushes and brushes containing P(M)AA segments. First, we review different surface-initiated polymerization (SIP) methods, with a focus on recent progress in the surface-initiated controlled/living radical polymerization (SI-CLRP) techniques used to generate P(M)AA brushes with a tailored structure. Next, we discuss biomolecule immobilization methods for P(M)AA brushes, including physical adsorption, covalent binding, and affinity interactions. Finally, typical biomedical applications of P(M)AA brushes are reviewed, and their performance is discussed based on their unique properties. We conclude that P(M)AA brushes are promising biomaterials, and more potential biomedical applications are expected to emerge with the further development of synthetic techniques and increased understanding of their interactions with biological systems.

Public data and open source tools for multi-assay genomic investigation of disease.

PubMed

Kannan, Lavanya; Ramos, Marcel; Re, Angela; El-Hachem, Nehme; Safikhani, Zhaleh; Gendoo, Deena M A; Davis, Sean; Gomez-Cabrero, David; Castelo, Robert; Hansen, Kasper D; Carey, Vincent J; Morgan, Martin; Culhane, Aedín C; Haibe-Kains, Benjamin; Waldron, Levi

2016-07-01

Molecular interrogation of a biological sample through DNA sequencing, RNA and microRNA profiling, proteomics and other assays, has the potential to provide a systems level approach to predicting treatment response and disease progression, and to developing precision therapies. Large publicly funded projects have generated extensive and freely available multi-assay data resources; however, bioinformatic and statistical methods for the analysis of such experiments are still nascent. We review multi-assay genomic data resources in the areas of clinical oncology, pharmacogenomics and other perturbation experiments, population genomics and regulatory genomics and other areas, and tools for data acquisition. Finally, we review bioinformatic tools that are explicitly geared toward integrative genomic data visualization and analysis. This review provides starting points for accessing publicly available data and tools to support development of needed integrative methods. © The Author 2015. Published by Oxford University Press.

Cardiac tissue engineering: state of the art.

PubMed

Hirt, Marc N; Hansen, Arne; Eschenhagen, Thomas

2014-01-17

The engineering of 3-dimensional (3D) heart muscles has undergone exciting progress for the past decade. Profound advances in human stem cell biology and technology, tissue engineering and material sciences, as well as prevascularization and in vitro assay technologies make the first clinical application of engineered cardiac tissues a realistic option and predict that cardiac tissue engineering techniques will find widespread use in the preclinical research and drug development in the near future. Tasks that need to be solved for this purpose include standardization of human myocyte production protocols, establishment of simple methods for the in vitro vascularization of 3D constructs and better maturation of myocytes, and, finally, thorough definition of the predictive value of these methods for preclinical safety pharmacology. The present article gives an overview of the present state of the art, bottlenecks, and perspectives of cardiac tissue engineering for cardiac repair and in vitro testing.

Multiagent cooperation and competition with deep reinforcement learning

PubMed Central

Kodelja, Dorian; Kuzovkin, Ilya; Korjus, Kristjan; Aru, Juhan; Aru, Jaan; Vicente, Raul

2017-01-01

Evolution of cooperation and competition can appear when multiple adaptive agents share a biological, social, or technological niche. In the present work we study how cooperation and competition emerge between autonomous agents that learn by reinforcement while using only their raw visual input as the state representation. In particular, we extend the Deep Q-Learning framework to multiagent environments to investigate the interaction between two learning agents in the well-known video game Pong. By manipulating the classical rewarding scheme of Pong we show how competitive and collaborative behaviors emerge. We also describe the progression from competitive to collaborative behavior when the incentive to cooperate is increased. Finally we show how learning by playing against another adaptive agent, instead of against a hard-wired algorithm, results in more robust strategies. The present work shows that Deep Q-Networks can become a useful tool for studying decentralized learning of multiagent systems coping with high-dimensional environments. PMID:28380078

Rolling Shutter Effect aberration compensation in Digital Holographic Microscopy

NASA Astrophysics Data System (ADS)

Monaldi, Andrea C.; Romero, Gladis G.; Cabrera, Carlos M.; Blanc, Adriana V.; Alanís, Elvio E.

2016-05-01

Due to the sequential-readout nature of most CMOS sensors, each row of the sensor array is exposed at a different time, resulting in the so-called rolling shutter effect that induces geometric distortion to the image if the video camera or the object moves during image acquisition. Particularly in digital holograms recording, while the sensor captures progressively each row of the hologram, interferometric fringes can oscillate due to external vibrations and/or noises even when the object under study remains motionless. The sensor records each hologram row in different instants of these disturbances. As a final effect, phase information is corrupted, distorting the reconstructed holograms quality. We present a fast and simple method for compensating this effect based on image processing tools. The method is exemplified by holograms of microscopic biological static objects. Results encourage incorporating CMOS sensors over CCD in Digital Holographic Microscopy due to a better resolution and less expensive benefits.

Computational approaches to substrate-based cell motility

DOE PAGES

Ziebert, Falko; Aranson, Igor S.

2016-07-15

Substrate-based crawling motility of eukaryotic cells is essential for many biological functions, both in developing and mature organisms. Motility dysfunctions are involved in several life-threatening pathologies such as cancer and metastasis. Motile cells are also a natural realization of active, self-propelled ‘particles’, a popular research topic in nonequilibrium physics. Finally, from the materials perspective, assemblies of motile cells and evolving tissues constitute a class of adaptive self-healing materials that respond to the topography, elasticity, and surface chemistry of the environment and react to external stimuli. Although a comprehensive understanding of substrate-based cell motility remains elusive, progress has been achieved recentlymore » in its modeling on the whole cell level. Furthermore we survey the most recent advances in computational approaches to cell movement and demonstrate how these models improve our understanding of complex self-organized systems such as living cells.« less

Demographic Analysis from Biometric Data: Achievements, Challenges, and New Frontiers.

PubMed

Sun, Yunlian; Zhang, Man; Sun, Zhenan; Tan, Tieniu

2018-02-01

Biometrics is the technique of automatically recognizing individuals based on their biological or behavioral characteristics. Various biometric traits have been introduced and widely investigated, including fingerprint, iris, face, voice, palmprint, gait and so forth. Apart from identity, biometric data may convey various other personal information, covering affect, age, gender, race, accent, handedness, height, weight, etc. Among these, analysis of demographics (age, gender, and race) has received tremendous attention owing to its wide real-world applications, with significant efforts devoted and great progress achieved. This survey first presents biometric demographic analysis from the standpoint of human perception, then provides a comprehensive overview of state-of-the-art advances in automated estimation from both academia and industry. Despite these advances, a number of challenging issues continue to inhibit its full potential. We second discuss these open problems, and finally provide an outlook into the future of this very active field of research by sharing some promising opportunities.

Hsp70: a chaperokine.

PubMed

Asea, Alexzander

2008-01-01

Chaperokine is a term recently coined to better describe the dual role of extracellular heat shock protein as both chaperone and cytokine. The augmentation of intracellular Hsp72 expression has clearly been demonstrated to be cytoprotective; with the ability to activate anti-apoptotic and anti-inflammatory pathways, exerting inhibitory effects on cell cycle progression and suppressing genes important in proliferation and differentiation. On the other hand, the role of extracellular Hsp72 is only now being elucidated and has been demonstrated to play a cytostimulatory role by enhancing proinflammatory cytokine and chemokine synthesis, up-regulate co-stimulatory molecule expression, enhance the maturation of dendritic cells and promote antitumour surveillance. This paper covers the most recent advances in elucidation of the mechanism by which the chaperokine activity of Hsp72 is transduced, addresses its biological significance and, finally, covers how it is being harnessed to produce novel therapeutic agents.

Synergy of understanding dermatologic disease and epidermal biology.

PubMed

Stanley, John R

2012-02-01

Dermatologic disease, although seldom life threatening, can be extremely disfiguring and interfere with the quality of life. In addition, as opposed to other organs, just the aging of skin and its adnexal structure the hair follicle can result in cosmetic concerns that affect most of us. The articles in this dermatology Review Series demonstrate recent progress in understanding the cell biology and molecular pathophysiology of the epidermis and hair follicles, which harbor keratinocyte and melanocyte stem cells. They reveal a dynamic relationship between research and clinical care: knowledge of dermatologic disease has facilitated the understanding of the biology of the epidermis and, in turn, progress in basic science has informed our understanding of disease. This type of synergy is a profound strength of clinical research of the type that the JCI is dedicated to publishing.

Biology Division. Progress report, August 1, 1982-September 30, 1983

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

Not Available

1984-01-01

The Biology Division is the component of the Oak Ridge National Laboratory that investigates the potential adverse health effects of energy-related substances. The body of this report provides summaries of the aims, scope and progress of the research of groups of investigators in the Division during the period of August 1, 1982, through September 30, 1983. At the end of each summary is a list of publications covering the same period (published or accepted for publication). For convenience, the summaries are assembled under Sections in accordance with the current organizational structure of the Biology Division; each Section begins with anmore » overview. It will be apparent, however, that currents run throughout the Division and that the various programs support and interact with each other.« less

The fundamental role of mechanical properties in the progression of cancer disease and inflammation

NASA Astrophysics Data System (ADS)

Mierke, Claudia Tanja

2014-07-01

The role of mechanical properties in cancer disease and inflammation is still underinvestigated and even ignored in many oncological and immunological reviews. In particular, eight classical hallmarks of cancer have been proposed, but they still ignore the mechanics behind the processes that facilitate cancer progression. To define the malignant transformation of neoplasms and finally reveal the functional pathway that enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific mechanical properties of cancer cells and their microenvironment such as the extracellular matrix as well as embedded cells such as fibroblasts, macrophages or endothelial cells. Thus, this review will present current cancer research from a biophysical point of view and will therefore focus on novel physical aspects and biophysical methods to investigate the aggressiveness of cancer cells and the process of inflammation. As cancer or immune cells are embedded in a certain microenvironment such as the extracellular matrix, the mechanical properties of this microenvironment cannot be neglected, and alterations of the microenvironment may have an impact on the mechanical properties of the cancer or immune cells. Here, it is highlighted how biophysical approaches, both experimental and theoretical, have an impact on the classical hallmarks of cancer and inflammation. It is even pointed out how these biophysical approaches contribute to the understanding of the regulation of cancer disease and inflammatory responses after tissue injury through physical microenvironmental property sensing mechanisms. The recognized physical signals are transduced into biochemical signaling events that guide cellular responses, such as malignant tumor progression, after the transition of cancer cells from an epithelial to a mesenchymal phenotype or an inflammatory response due to tissue injury. Moreover, cell adaptation to mechanical alterations, in particular the understanding of mechano-coupling and mechano-regulating functions in cell invasion, appears as an important step in cancer progression and inflammatory response to injuries. This may lead to novel insights into cancer disease and inflammatory diseases and will overcome classical views on cancer and inflammation. In addition, this review will discuss how the physics of cancer and inflammation can help to reveal whether cancer cells will invade connective tissue and metastasize or how leukocytes extravasate and migrate through the tissue. In this review, the physical concepts of cancer progression, including the tissue basement membrane a cancer cell is crossing, its invasion and transendothelial migration as well as the basic physical concepts of inflammatory processes and the cellular responses to the mechanical stress of the microenvironment such as external forces and matrix stiffness, are presented and discussed. In conclusion, this review will finally show how physical measurements can improve classical approaches that investigate cancer and inflammatory diseases, and how these physical insights can be integrated into classical tumor biological approaches.

Radiation physics, biophysics and radiation biology. Progress report for October 1, 1979-September 30, 1980. [Lead abstract

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

Rossi, H.H.; Hall, E.J.

1980-07-01

Separate abstracts were prepared for 31 of the 32 papers presented in this progress report. The other paper is represented by an abstract only and deals with field shaping and recalibration of x-ray facilities.

Advances in insect physiology. Progress in mosquito research

USDA-ARS?s Scientific Manuscript database

This book review briefly summarizes the most interesting topics/chapters from the book: "Advances in Insect Physiology: Progress in mosquito Research". The book is an excellent overview of the recent advances in mosquito biology. This volume encompasses 13 chapters from 32 contributing authors who ...

Education from a Biological Point of View

ERIC Educational Resources Information Center

Boulter, Stephen

2017-01-01

There appears to be an irresolvable disagreement between "progressives" and "conservatives" regarding the ultimate aims of education. This paper argues that the dispute is irresolvable as it currently stands because the traditional progressive/conservative dichotomies are false and based on distorted half-truths. The current…

Mechanobiology by the numbers: a close relationship between biology and physics.

PubMed

Schwarz, Ulrich S

2017-12-01

Studies of mechanobiology lie at the interface of various scientific disciplines from biology to physics. Accordingly, quantification and mathematical modelling have been instrumental in fuelling the progress in this rapidly developing research field, assisting experimental work on many levels.

Trypanosoma cruzi DTU TcII presents higher blood parasitism than DTU TcI in an experimental model of mixed infection.

PubMed

Sales-Campos, Helioswilton; Kappel, Henrique Borges; Andrade, Cristiane Pontes; Lima, Tiago Pereira; de Castilho, Alessandra; Giraldo, Luis Eduardo Ramirez; Lages-Silva, Eliane

2015-09-01

Trypanosoma cruzi (Tc), the causative agent of Chagas disease, affects millions of people worldwide. One of the major characteristics of T. cruzi is related to its heterogeneity due to the variability of its biological properties, parasite growth rates, infectivity, tissue tropism, morbidity and virulence among different isolates observed during experimental or human infection. Moreover, presence of mixed infections in the same host in endemic areas is a matter of study due to its impact on clinical manifestations and disease progression. In this study, we evaluated the biological behavior of two Tc I strains AQ1-7 (AQ) and MUTUM (MT) and one Tc II strain (JG) during the acute phase of infection, in unique and mixed infections. A patent blood parasitism was detected only in mice inoculated with JG strain . In addition blood parasitism parameters (peak and average blood parasitism) were positively associated when JG and AQ strains were combined. In contrast, a negative association was observed in the JG+MUTUM group. The predominance of TcII strain over TcI strains was highlighted using the LSSP-PCR technique, which was performed in samples from hemoculture. Thus, this study showed important biological differences between different T. cruzi strains and discrete typing units (DTUs) in acute phase. Finally, we observed that blood parasitism during early period of infection seems to be more related to DTU than to a specific strain.

Lantibiotic engineering: molecular characterization and exploitation of lantibiotic-synthesizing enzymes for peptide engineering.

PubMed

Nagao, Jun-ichi; Aso, Yuji; Shioya, Kouki; Nakayama, Jiro; Sonomoto, Kenji

2007-01-01

Lanthionine-containing peptide antibiotics called lantibiotics are produced by a large number of Gram-positive bacteria. Nukacin ISK-1 produced by Staphylococcus warneri ISK-1 is type-A(II) lantibiotic. Ribosomally synthesized nukacin ISK-1 prepeptide (NukA) consists of an N-terminal leader peptide followed by a C-terminal propeptide moiety that undergoes several post-translational modification events including unusual amino acid formation by the modification enzyme NukM, cleavage of leader peptide and export by the dual functional ABC transporter NukT, finally yielding a biologically active peptide. Unusual amino acids in lantibiotics contribute to biological activity and also structural stability against proteases. Thus, lantibiotic-synthesizing enzymes have a high potentiality for peptide engineering by introduction of unusual amino acids into desired peptides with altering biological and physicochemical properties, e.g., activity and stability, termed lantibiotic engineering. We report the establishment of a heterologous expression of nukacin ISK-1 biosynthetic gene cluster by the nisin-controlled expression system and discuss our recent progress in understanding of the biosynthetic enzymes for nukacin ISK-1 such as localization, molecular interaction in biophysical and biochemical aspects. Substrate specificity of the lantibiotic-synthesizing enzymes was evaluated by complementation of the biosynthetic enzymes (LctM and LctT) of closely related lantibiotic lacticin 481 for nukacin ISK-1 biosynthesis. We further explored a rapid and powerful tool for introduction of unusual amino acids by co-expression of hexa-histidine-tagged NukA and NukM in Escherichia coli.

Advances in the genetic dissection of plant cell walls: tools and resources available in Miscanthus

PubMed Central

Slavov, Gancho; Allison, Gordon; Bosch, Maurice

2013-01-01

Tropical C4 grasses from the genus Miscanthus are believed to have great potential as biomass crops. However, Miscanthus species are essentially undomesticated, and genetic, molecular and bioinformatics tools are in very early stages of development. Furthermore, similar to other crops targeted as lignocellulosic feedstocks, the efficient utilization of biomass is hampered by our limited knowledge of the structural organization of the plant cell wall and the underlying genetic components that control this organization. The Institute of Biological, Environmental and Rural Sciences (IBERS) has assembled an extensive collection of germplasm for several species of Miscanthus. In addition, an integrated, multidisciplinary research programme at IBERS aims to inform accelerated breeding for biomass productivity and composition, while also generating fundamental knowledge. Here we review recent advances with respect to the genetic characterization of the cell wall in Miscanthus. First, we present a summary of recent and on-going biochemical studies, including prospects and limitations for the development of powerful phenotyping approaches. Second, we review current knowledge about genetic variation for cell wall characteristics of Miscanthus and illustrate how phenotypic data, combined with high-density arrays of single-nucleotide polymorphisms, are being used in genome-wide association studies to generate testable hypotheses and guide biological discovery. Finally, we provide an overview of the current knowledge about the molecular biology of cell wall biosynthesis in Miscanthus and closely related grasses, discuss the key conceptual and technological bottlenecks, and outline the short-term prospects for progress in this field. PMID:23847628

Biosecurity and Open-Source Biology: The Promise and Peril of Distributed Synthetic Biological Technologies.

PubMed

Evans, Nicholas G; Selgelid, Michael J

2015-08-01

In this article, we raise ethical concerns about the potential misuse of open-source biology (OSB): biological research and development that progresses through an organisational model of radical openness, deskilling, and innovation. We compare this organisational structure to that of the open-source software model, and detail salient ethical implications of this model. We demonstrate that OSB, in virtue of its commitment to openness, may be resistant to governance attempts.

Racing of the biological pacemaker.

PubMed

Yu, Han-Gang

2009-01-01

Over the past decade, rapid progress in the molecular studies of cardiac ion channels and stem cells biology has led to efforts to create a biological pacemaker to supplement the widely-used electronic pacemaker. We will review the main concepts of cardiac pacemaker activities in different heart regions and the approaches to design a working biological pacemaker. We will focus on how to use the gene- and cell-based approaches to meet the requirements of a working biological pacemaker. Possible future development and precautions for creation of an effective biological pacemaker superior to the electronic counterpart are also discussed along with recent patents.

Recent progress of highly efficient in vivo biological screening for novel agrochemicals in China.

PubMed

Li, Baoju; Yuan, Huizhu; Fang, Jichao; Tao, Liming; Huang, Qingchun; Qian, Xuhong; Fan, Zhijin

2010-03-01

This paper describes the recent progress of in vivo biological screening for pesticides in China. According to the criteria, including the severity of damage caused by pests and the economic value of the crops, the investigated insects, pathogens, herbs and other species in the agricultural field were selected as the main screening targets for pesticides. Corresponding in vivo microscreening methods have been established and applied in the pesticide screening procedure, which has higher reproducibility, a shorter time and greater efficiency that offset the drawbacks of conventional methods for pesticide screening.

Revolution of Alzheimer Precision Neurology Passageway of Systems Biology and Neurophysiology.

PubMed

Hampel, Harald; Toschi, Nicola; Babiloni, Claudio; Baldacci, Filippo; Black, Keith L; Bokde, Arun L W; Bun, René S; Cacciola, Francesco; Cavedo, Enrica; Chiesa, Patrizia A; Colliot, Olivier; Coman, Cristina-Maria; Dubois, Bruno; Duggento, Andrea; Durrleman, Stanley; Ferretti, Maria-Teresa; George, Nathalie; Genthon, Remy; Habert, Marie-Odile; Herholz, Karl; Koronyo, Yosef; Koronyo-Hamaoui, Maya; Lamari, Foudil; Langevin, Todd; Lehéricy, Stéphane; Lorenceau, Jean; Neri, Christian; Nisticò, Robert; Nyasse-Messene, Francis; Ritchie, Craig; Rossi, Simone; Santarnecchi, Emiliano; Sporns, Olaf; Verdooner, Steven R; Vergallo, Andrea; Villain, Nicolas; Younesi, Erfan; Garaci, Francesco; Lista, Simone

2018-03-16

The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular, and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an "omics"-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical, and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer's disease. The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group "Alzheimer Precision Medicine" (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development toward breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND.

Revolution of Alzheimer Precision Neurology: Passageway of Systems Biology and Neurophysiology

PubMed Central

Hampel, Harald; Toschi, Nicola; Babiloni, Claudio; Baldacci, Filippo; Black, Keith L.; Bokde, Arun L.W.; Bun, René S.; Cacciola, Francesco; Cavedo, Enrica; Chiesa, Patrizia A.; Colliot, Olivier; Coman, Cristina-Maria; Dubois, Bruno; Duggento, Andrea; Durrleman, Stanley; Ferretti, Maria-Teresa; George, Nathalie; Genthon, Remy; Habert, Marie-Odile; Herholz, Karl; Koronyo, Yosef; Koronyo-Hamaoui, Maya; Lamari, Foudil; Langevin, Todd; Lehéricy, Stéphane; Lorenceau, Jean; Neri, Christian; Nisticò, Robert; Nyasse-Messene, Francis; Ritchie, Craig; Rossi, Simone; Santarnecchi, Emiliano; Sporns, Olaf; Verdooner, Steven R.; Vergallo, Andrea; Villain, Nicolas; Younesi, Erfan; Garaci, Francesco; Lista, Simone

2018-01-01

The Precision Neurology development process implements systems theory with system biology and neurophysiology in a parallel, bidirectional research path: a combined hypothesis-driven investigation of systems dysfunction within distinct molecular, cellular and large-scale neural network systems in both animal models as well as through tests for the usefulness of these candidate dynamic systems biomarkers in different diseases and subgroups at different stages of pathophysiological progression. This translational research path is paralleled by an “omics”-based, hypothesis-free, exploratory research pathway, which will collect multimodal data from progressing asymptomatic, preclinical and clinical neurodegenerative disease (ND) populations, within the wide continuous biological and clinical spectrum of ND, applying high-throughput and high-content technologies combined with powerful computational and statistical modeling tools, aimed at identifying novel dysfunctional systems and predictive marker signatures associated with ND. The goals are to identify common biological denominators or differentiating classifiers across the continuum of ND during detectable stages of pathophysiological progression, characterize systems-based intermediate endophenotypes, validate multi-modal novel diagnostic systems biomarkers, and advance clinical intervention trial designs by utilizing systems-based intermediate endophenotypes and candidate surrogate markers. Achieving these goals is key to the ultimate development of early and effective individualized treatment of ND, such as Alzheimer’s disease (AD). The Alzheimer Precision Medicine Initiative (APMI) and cohort program (APMI-CP), as well as the Paris based core of the Sorbonne University Clinical Research Group “Alzheimer Precision Medicine” (GRC-APM) were recently launched to facilitate the passageway from conventional clinical diagnostic and drug development towards breakthrough innovation based on the investigation of the comprehensive biological nature of aging individuals. The APMI movement is gaining momentum to systematically apply both systems neurophysiology and systems biology in exploratory translational neuroscience research on ND. PMID:29562524

Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.

PubMed

Castellanos, Emily H; Horn, Leora

2016-06-01

: The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease. ©AlphaMed Press.

Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

PubMed Central

Castellanos, Emily H.

2016-01-01

The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. Implications for Practice: The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease. PMID:27053502

Protein-protein interaction analysis of Alzheimer`s disease and NAFLD based on systems biology methods unhide common ancestor pathways.

PubMed

Karbalaei, Reza; Allahyari, Marzieh; Rezaei-Tavirani, Mostafa; Asadzadeh-Aghdaei, Hamid; Zali, Mohammad Reza

2018-01-01

Analysis reconstruction networks from two diseases, NAFLD and Alzheimer`s diseases and their relationship based on systems biology methods. NAFLD and Alzheimer`s diseases are two complex diseases, with progressive prevalence and high cost for countries. There are some reports on relation and same spreading pathways of these two diseases. In addition, they have some similar risk factors, exclusively lifestyle such as feeding, exercises and so on. Therefore, systems biology approach can help to discover their relationship. DisGeNET and STRING databases were sources of disease genes and constructing networks. Three plugins of Cytoscape software, including ClusterONE, ClueGO and CluePedia, were used to analyze and cluster networks and enrichment of pathways. An R package used to define best centrality method. Finally, based on degree and Betweenness, hubs and bottleneck nodes were defined. Common genes between NAFLD and Alzheimer`s disease were 190 genes that used construct a network with STRING database. The resulting network contained 182 nodes and 2591 edges and comprises from four clusters. Enrichment of these clusters separately lead to carbohydrate metabolism, long chain fatty acid and regulation of JAK-STAT and IL-17 signaling pathways, respectively. Also seven genes selected as hub-bottleneck include: IL6, AKT1, TP53, TNF, JUN, VEGFA and PPARG. Enrichment of these proteins and their first neighbors in network by OMIM database lead to diabetes and obesity as ancestors of NAFLD and AD. Systems biology methods, specifically PPI networks, can be useful for analyzing complicated related diseases. Finding Hub and bottleneck proteins should be the goal of drug designing and introducing disease markers.

Network-based analysis of differentially expressed genes in cerebrospinal fluid (CSF) and blood reveals new candidate genes for multiple sclerosis

PubMed Central

Safari-Alighiarloo, Nahid; Taghizadeh, Mohammad; Tabatabaei, Seyyed Mohammad; Namaki, Saeed

2016-01-01

Background The involvement of multiple genes and missing heritability, which are dominant in complex diseases such as multiple sclerosis (MS), entail using network biology to better elucidate their molecular basis and genetic factors. We therefore aimed to integrate interactome (protein–protein interaction (PPI)) and transcriptomes data to construct and analyze PPI networks for MS disease. Methods Gene expression profiles in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from MS patients, sampled in relapse or remission and controls, were analyzed. Differentially expressed genes which determined only in CSF (MS vs. control) and PBMCs (relapse vs. remission) separately integrated with PPI data to construct the Query-Query PPI (QQPPI) networks. The networks were further analyzed to investigate more central genes, functional modules and complexes involved in MS progression. Results The networks were analyzed and high centrality genes were identified. Exploration of functional modules and complexes showed that the majority of high centrality genes incorporated in biological pathways driving MS pathogenesis. Proteasome and spliceosome were also noticeable in enriched pathways in PBMCs (relapse vs. remission) which were identified by both modularity and clique analyses. Finally, STK4, RB1, CDKN1A, CDK1, RAC1, EZH2, SDCBP genes in CSF (MS vs. control) and CDC37, MAP3K3, MYC genes in PBMCs (relapse vs. remission) were identified as potential candidate genes for MS, which were the more central genes involved in biological pathways. Discussion This study showed that network-based analysis could explicate the complex interplay between biological processes underlying MS. Furthermore, an experimental validation of candidate genes can lead to identification of potential therapeutic targets. PMID:28028462

Physical Biology of Axonal Damage.

PubMed

de Rooij, Rijk; Kuhl, Ellen

2018-01-01

Excessive physical impacts to the head have direct implications on the structural integrity at the axonal level. Increasing evidence suggests that tau, an intrinsically disordered protein that stabilizes axonal microtubules, plays a critical role in the physical biology of axonal injury. However, the precise mechanisms of axonal damage remain incompletely understood. Here we propose a biophysical model of the axon to correlate the dynamic behavior of individual tau proteins under external physical forces to the evolution of axonal damage. To propagate damage across the scales, we adopt a consistent three-step strategy: First, we characterize the axonal response to external stretches and stretch rates for varying tau crosslink bond strengths using a discrete axonal damage model. Then, for each combination of stretch rates and bond strengths, we average the axonal force-stretch response of n = 10 discrete simulations, from which we derive and calibrate a homogenized constitutive model. Finally, we embed this homogenized model into a continuum axonal damage model of [1-d]-type in which d is a scalar damage parameter that is driven by the axonal stretch and stretch rate. We demonstrate that axonal damage emerges naturally from the interplay of physical forces and biological crosslinking. Our study reveals an emergent feature of the crosslink dynamics: With increasing loading rate, the axonal failure stretch increases, but axonal damage evolves earlier in time. For a wide range of physical stretch rates, from 0.1 to 10 /s, and biological bond strengths, from 1 to 100 pN, our model predicts a relatively narrow window of critical damage stretch thresholds, from 1.01 to 1.30, which agrees well with experimental observations. Our biophysical damage model can help explain the development and progression of axonal damage across the scales and will provide useful guidelines to identify critical damage level thresholds in response to excessive physical forces.

Biological properties

Treesearch

Rebecca E. Ibach

2005-01-01

There are numerous biological degradations that wood is exposed to in various environments. Biological damage occurs when a log, sawn product, or final product is not stored, handled, or designed properly. Biological organisms, such as bacteria, mold, stain, decay fungi, insects, and marine borers, depend heavily on temperature and moisture conditions to grow. A higher...

Health and Safety Research Division progress report, April 1, 1981-September 30, 1982

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

Not Available

1983-02-01

Research progress for the reporting period is briefly summarized for the following sections: (1) health studies, (2) technology assessments, (3) biological and radiation physics, (4) chemical physics, (5) Office of Risk Analysis, and (6) health and environmental risk and analysis. (ACR)

Building bridges between the physical and biological sciences.

PubMed

Ninham, B W; Boström, M

2005-12-16

This paper attempts to identify major conceptual issues that have inhibited the application of physical chemistry to problems in the biological sciences. We will trace out where theories went wrong, how to repair the present foundations, and discuss current progress toward building a better dialogue.

Pancreatic cancer stromal biology and therapy

PubMed Central

Xie, Dacheng; Xie, Keping

2015-01-01

Pancreatic cancer is one of the most lethal malignancies. Significant progresses have been made in understanding of pancreatic cancer pathogenesis, including appreciation of precursor lesions or premalignant pancreatic intraepithelial neoplasia (PanINs), description of sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and identification of major genetic and epigenetic events and the biological impact of those events on malignant behavior. However, the currently used therapeutic strategies targeting tumor epithelial cells, which are potent in cell culture and animal models, have not been successful in the clinic. Presumably, therapeutic resistance of pancreatic cancer is at least in part due to its drastic desmoplasis, which is a defining hallmark for and circumstantially contributes to pancreatic cancer development and progression. Improved understanding of the dynamic interaction between cancer cells and the stroma is important to better understanding pancreatic cancer biology and to designing effective intervention strategies. This review focuses on the origination, evolution and disruption of stromal molecular and cellular components in pancreatic cancer, and their biological effects on pancreatic cancer pathogenesis. PMID:26114155

The role of low-grade inflammation and metabolic flexibility in aging and nutritional modulation thereof: a systems biology approach.

PubMed

Calçada, Dulce; Vianello, Dario; Giampieri, Enrico; Sala, Claudia; Castellani, Gastone; de Graaf, Albert; Kremer, Bas; van Ommen, Ben; Feskens, Edith; Santoro, Aurelia; Franceschi, Claudio; Bouwman, Jildau

2014-01-01

Aging is a biological process characterized by the progressive functional decline of many interrelated physiological systems. In particular, aging is associated with the development of a systemic state of low-grade chronic inflammation (inflammaging), and with progressive deterioration of metabolic function. Systems biology has helped in identifying the mediators and pathways involved in these phenomena, mainly through the application of high-throughput screening methods, valued for their molecular comprehensiveness. Nevertheless, inflammation and metabolic regulation are dynamical processes whose behavior must be understood at multiple levels of biological organization (molecular, cellular, organ, and system levels) and on multiple time scales. Mathematical modeling of such behavior, with incorporation of mechanistic knowledge on interactions between inflammatory and metabolic mediators, may help in devising nutritional interventions capable of preventing, or ameliorating, the age-associated functional decline of the corresponding systems. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Removing the tree-ring width biological trend using expected basal area increment

Treesearch

Franco Biondi; Fares Qeadan

2008-01-01

One of the main elements of dendrochronological standardization is the removal of the biological trend, i.e., the progressive decline of ring width along a cross-sectional radius that is mostly caused by the corresponding increase in stem diameter over time. A very common option for removing this biological trend is to fit a modified negative exponential curve to the...

The complexities of skeletal biology

NASA Technical Reports Server (NTRS)

Karsenty, Gerard

2003-01-01

For a long time, the skeleton was seen as an amorphous tissue of little biological interest. But such a view ignored the large number of genetic and degenerative diseases affecting this organ. Over the past 15 years, molecular and genetic studies have modified our understanding of skeletal biology. By so doing this progress has affected our understanding of diseases and suggested in many instances new therapeutic opportunities.

Methionine Sulfoxide Reductase A Knockout Mice Show Progressive Hearing Loss and Sensitivity to Acoustic Trauma.

PubMed

Alqudah, Safa; Chertoff, Mark; Durham, Dianne; Moskovitz, Jackob; Staecker, Hinrich; Peppi, Marcello

2018-06-21

Methionine sulfoxide reductases (MsrA and MsrB) protect the biological activity of proteins from oxidative modifications to methionine residues and are important for protecting against the pathological effects of neurodegenerative diseases. In the current study, we characterized the auditory phenotype of the MsrA knockout mouse. Young MsrA knockout mice showed small high-frequency threshold elevations for auditory brainstem response and distortion product otoacoustic emission compared to those of wild-type mice, which progressively worsened in older MsrA knockout mice. MsrA knockout mice showed an increased sensitivity to noise at young and older ages, suggesting that MsrA is part of a mechanism that protects the cochlea from acoustic damage. MsrA mRNA in the cochlea was increased following acoustic stimulation. Finally, expression of mRNA MsrB1 was compromised at 6 months old, but not in younger MsrA knockout mice (compared to controls). The identification of MsrA in the cochlea as a protective mediator from both early onset hearing loss and acoustic trauma expands our understanding of the pathways that may induce protection from acoustic trauma and foster further studies on how to prevent the damaging effect of noise exposure through Msr-based therapy. © 2018 S. Karger AG, Basel.

Project 1: Microbial Genomes: A Genomic Approach to Understanding the Evolution of Virulence. Project 2: From Genomes to Life: Drosophilia Development in Space and Time

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

Robert DeSalle

2004-09-10

This project seeks to use the genomes of two close relatives, A. actinomycetemcomitans and H. aphrophilus, to understand the evolutionary changes that take place in a genome to make it more or less virulent. Our primary specific aim of this project was to sequence, annotate, and analyze the genomes of Actinobacillus actinomycetemcomitans (CU1000, serotype f) and Haemophilus aphrophilus. With these genome sequences we have then compared the whole genome sequences to each other and to the current Aa (HK1651 www.genome.ou.edu) genome project sequence along with other fully sequenced Pasteurellaceae to determine inter and intra species differences that may account formore » the differences and similarities in disease. We also propose to create and curate a comprehensive database where sequence information and analysis for the Pasteurellaceae (family that includes the genera Actinobacillus and Haemophilus) are readily accessible. And finally we have proposed to develop phylogenetic techniques that can be used to efficiently and accurately examine the evolution of genomes. Below we report on progress we have made on these major specific aims. Progress on the specific aims is reported below under two major headings--experimental approaches and bioinformatics and systematic biology approaches.« less

Tissue Regeneration in the Chronically Inflamed Tumor Environment: Implications for Cell Fusion Driven Tumor Progression and Therapy Resistant Tumor Hybrid Cells

PubMed Central

Dittmar, Thomas; Zänker, Kurt S.

2015-01-01

The biological phenomenon of cell fusion in a cancer context is still a matter of controversial debates. Even though a plethora of in vitro and in vivo data have been published in the past decades the ultimate proof that tumor hybrid cells could originate in (human) cancers and could contribute to the progression of the disease is still missing, suggesting that the cell fusion hypothesis is rather fiction than fact. However, is the lack of this ultimate proof a valid argument against this hypothesis, particularly if one has to consider that appropriate markers do not (yet) exist, thus making it virtually impossible to identify a human tumor cell clearly as a tumor hybrid cell. In the present review, we will summarize the evidence supporting the cell fusion in cancer concept. Moreover, we will refine the cell fusion hypothesis by providing evidence that cell fusion is a potent inducer of aneuploidy, genomic instability and, most likely, even chromothripsis, suggesting that cell fusion, like mutations and aneuploidy, might be an inducer of a mutator phenotype. Finally, we will show that “accidental” tissue repair processes during cancer therapy could lead to the origin of therapy resistant cancer hybrid stem cells. PMID:26703575

Tissue Regeneration in the Chronically Inflamed Tumor Environment: Implications for Cell Fusion Driven Tumor Progression and Therapy Resistant Tumor Hybrid Cells.

PubMed

Dittmar, Thomas; Zänker, Kurt S

2015-12-19

The biological phenomenon of cell fusion in a cancer context is still a matter of controversial debates. Even though a plethora of in vitro and in vivo data have been published in the past decades the ultimate proof that tumor hybrid cells could originate in (human) cancers and could contribute to the progression of the disease is still missing, suggesting that the cell fusion hypothesis is rather fiction than fact. However, is the lack of this ultimate proof a valid argument against this hypothesis, particularly if one has to consider that appropriate markers do not (yet) exist, thus making it virtually impossible to identify a human tumor cell clearly as a tumor hybrid cell. In the present review, we will summarize the evidence supporting the cell fusion in cancer concept. Moreover, we will refine the cell fusion hypothesis by providing evidence that cell fusion is a potent inducer of aneuploidy, genomic instability and, most likely, even chromothripsis, suggesting that cell fusion, like mutations and aneuploidy, might be an inducer of a mutator phenotype. Finally, we will show that "accidental" tissue repair processes during cancer therapy could lead to the origin of therapy resistant cancer hybrid stem cells.

Terahertz detectors and focal plane arrays

NASA Astrophysics Data System (ADS)

Rogalski, A.; Sizov, F.

2011-09-01

Terahertz (THz) technology is one of emerging technologies that will change our life. A lot of attractive applications in security, medicine, biology, astronomy, and non-destructive materials testing have been demonstrated already. However, the realization of THz emitters and receivers is a challenge because the frequencies are too high for conventional electronics and the photon energies are too small for classical optics. As a result, THz radiation is resistant to the techniques commonly employed in these well established neighbouring bands. In the paper, issues associated with the development and exploitation of THz radiation detectors and focal plane arrays are discussed. Historical impressive progress in THz detector sensitivity in a period of more than half century is analyzed. More attention is put on the basic physical phenomena and the recent progress in both direct and heterodyne detectors. After short description of general classification of THz detectors, more details concern Schottky barrier diodes, pair braking detectors, hot electron mixers and field-effect transistor detectors, where links between THz devices and modern technologies such as micromachining are underlined. Also, the operational conditions of THz detectors and their upper performance limits are reviewed. Finally, recent advances in novel nanoelectronic materials and technologies are described. It is expected that applications of nanoscale materials and devices will open the door for further performance improvement in THz detectors.

Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease.

PubMed

Carrasquillo, Minerva M; Crook, Julia E; Pedraza, Otto; Thomas, Colleen S; Pankratz, V Shane; Allen, Mariet; Nguyen, Thuy; Malphrus, Kimberly G; Ma, Li; Bisceglio, Gina D; Roberts, Rosebud O; Lucas, John A; Smith, Glenn E; Ivnik, Robert J; Machulda, Mary M; Graff-Radford, Neill R; Petersen, Ronald C; Younkin, Steven G; Ertekin-Taner, Nilüfer

2015-01-01

We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM-rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Argonaute: The executor of small RNA function.

PubMed

Azlan, Azali; Dzaki, Najat; Azzam, Ghows

2016-08-20

The discovery of small non-coding RNAs - microRNA (miRNA), short interfering RNA (siRNA) and PIWI-interacting RNA (piRNA) - represents one of the most exciting frontiers in biology specifically on the mechanism of gene regulation. In order to execute their functions, these small RNAs require physical interactions with their protein partners, the Argonaute (AGO) family proteins. Over the years, numerous studies have made tremendous progress on understanding the roles of AGO in gene silencing in various organisms. In this review, we summarize recent progress of AGO-mediated gene silencing and other cellular processes in which AGO proteins have been implicated with a particular focus on progress made in flies, humans and other model organisms as compliment. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Progress towards personalized therapeutics: biologic- and risk-directed therapy for neuroblastoma.

PubMed

Gustafson, William Clay; Matthay, Katherine K

2011-10-01

Neuroblastoma, a tumor of the developing peripheral sympathetic nervous system, is the most common and deadly extracranial solid tumor of childhood. Risk-stratification and risk-adapted therapy play a large role in the modern treatment of neuroblastoma. Recently, through extensive international collaboration, new guidelines for risk stratification have emerged that will aid in international cooperative studies, as well as clarifying therapeutic options for patients. Current therapies for low- and intermediate-risk neuroblastoma have resulted in excellent prognoses for these risk strata, and current efforts are concentrated on chemotherapy reduction. By contrast, much more gradual progress has been made in improving survival for high-risk neuroblastoma patients, despite significant chemotherapy intensification. Current investigations focus on overcoming resistance by elucidating the molecular/genetic causes of neuroblastoma tumorigenesis and progression, with the aim of developing more effective biologically targeted therapies for this disease.

Deep remission: a new concept?

PubMed

Colombel, Jean-Frédéric; Louis, Edouard; Peyrin-Biroulet, Laurent; Sandborn, William J; Panaccione, Remo

2012-01-01

Crohn's disease (CD) is a chronic inflammatory disorder characterized by periods of clinical remission alternating with periods of relapse defined by recurrent clinical symptoms. Persistent inflammation is believed to lead to progressive bowel damage over time, which manifests with the development of strictures, fistulae and abscesses. These disease complications frequently lead to a need for surgical resection, which in turn leads to disability. So CD can be characterized as a chronic, progressive, destructive and disabling disease. In rheumatoid arthritis, treatment paradigms have evolved beyond partial symptom control alone toward the induction and maintenance of sustained biological remission, also known as a 'treat to target' strategy, with the goal of improving long-term disease outcomes. In CD, there is currently no accepted, well-defined, comprehensive treatment goal that entails the treatment of both clinical symptoms and biologic inflammation. It is important that such a treatment concept begins to evolve for CD. A treatment strategy that delays or halts the progression of CD to increasing damage and disability is a priority. As a starting point, a working definition of sustained deep remission (that includes long-term biological remission and symptom control) with defined patient outcomes (including no disease progression) has been proposed. The concept of sustained deep remission represents a goal for CD management that may still evolve. It is not clear if the concept also applies to ulcerative colitis. Clinical trials are needed to evaluate whether treatment algorithms that tailor therapy to achieve deep remission in patients with CD can prevent disease progression and disability. Copyright © 2012 S. Karger AG, Basel.

20 CFR 437.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Final request for payment (SF-270) (if applicable). (iv) Invention disclosure (if applicable). (v... are not limited to: (i) Final performance or progress report. (ii) Financial Status Report (SF 269) or...

Freshwater Biological Traits Database (Data Sources)

EPA Science Inventory

When EPA release the final report, Freshwater Biological Traits Database, it referenced numerous data sources that are included below. The Traits Database report covers the development of a database of freshwater biological traits with additional traits that are relevan...

Beware the tail that wags the dog: informal and formal models in biology

PubMed Central

Gunawardena, Jeremy

2014-01-01

Informal models have always been used in biology to guide thinking and devise experiments. In recent years, formal mathematical models have also been widely introduced. It is sometimes suggested that formal models are inherently superior to informal ones and that biology should develop along the lines of physics or economics by replacing the latter with the former. Here I suggest to the contrary that progress in biology requires a better integration of the formal with the informal. PMID:25368417

Biologic therapies in the treatment of sarcoidosis.

PubMed

Saketkoo, Lesley Ann; Baughman, Robert P

2016-08-01

Sarcoidosis is a disease of remarkable heterogeneity in organ manifestation, severity and natural history, characterized by the presence of non-caseating granulomas. The majority of cases are acute and self-limited or remit with short courses of glucocorticoids; however, a proportion progress to a life-threatening obliterative fibrotic type associated with significant disability related to pulmonary, cardiac, ocular or central nervous system involvement. Biologic agents have been demonstrated in the successful treatment of refractory organ-threatening sarcoidosis; and though sarcoidosis remains elusive in predictability of progression, strong evidence suggests an indisputably efficacious role for these agents in efforts to stave morbidity and mortality related to sarcoidosis. This paper provides a review of sarcoidosis mechanistic etiopathogenesis to highlight the hypothetical underpinnings of the utility and concerns of current biologic treatments in current use and the potential future applications of newer agents and those under development.

45 CFR 1157.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-10-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

43 CFR 12.90 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-10-01

....) (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

49 CFR 18.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-10-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

45 CFR 1183.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-10-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

45 CFR 1174.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-10-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

28 CFR 66.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-07-01

....) (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

21 CFR 1403.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-04-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

22 CFR 135.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-04-01

...). (3) Final request for payment (SF-270) (if applicable). (4) Invention disclosure (if applicable). (5... include but are not limited to: (1) Final performance or progress report. (2) Financial Status Report (SF...

Biology Division annual progress report for period ending December 31, 1968

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

None

1969-07-01

Brief summaries are presented of research in progress in the fields of radiobiology, genetics, hematology, immunology, physsiology, biochemistry, bacteriology, enzymology, microbiology, photosynthesis, biophysics, radiation protection, and related fields. A list is included of 212 publications in the world literature that report results of completed studies. (CH)

Health and Safety Research Division. Progress report, October 1, 1979-March 31, 1981

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

Not Available

1981-08-01

Research progress for the period October 1, 1979 through March 31, 1981 is reported. Research conducted by the Office of Integrated Assessments and Policy Analysis, Health Studies Section, Technology Assessments Section, Biological and Radiation Physics Section, and Chemical Physics Section is summarized. (ACR)

Progressive Education Standards: A Neuroscience Framework

ERIC Educational Resources Information Center

O'Grady, Patty

2011-01-01

This paper proposes a coherent and unique set of 12 standards, adopting a neuroscience framework for biologically based on school reform. This model of educational principles and practices aligns with the long-standing principles and practices of the Progressive Education Movement in the United States and the emerging principles of neuroscience.…

Research on Disorders of the Mind. Progress & Prospects.

ERIC Educational Resources Information Center

National Inst. of Mental Health (DHEW), Rockville, MD.

The 14 conference papers on mental illness focus on the biological, genetic, psychopharmacological, psychopathological, and epidemiological and social factors related to psychoses. Divided into five sections each preceded by a brief introduction, entries include the following titles and authors: "The Biological Substrates of Schizophrenia" (S.…

Redox Biology Final Examination 2016 | Center for Cancer Research

Cancer.gov

Numerous registrants have requested a certificate upon completion of the Redox Biology (RB) course. In order to obtain a certificate, you must answer 8 of the 12 questions below correctly. In the final examination, 1 question is derived from each of the 1-hour lectures. It is highly recommended that you have a copy of each PowerPoint presentation prior to taking the examination.

Cueing Metacognition to Improve Researching and Essay Writing in a Final Year High School Biology Class

ERIC Educational Resources Information Center

Conner, L. N.

2007-01-01

This paper reports on degrees of awareness and use of specific metacognitive strategies by 16 students in a final-year high school biology class in New Zealand. The aims of the intervention were to broaden students' thinking about bioethical issues associated with cancer and to enhance students' use of metacognition. Cues and prompts were used in…

Redox Biology Final Examination 2016 | Center for Cancer Research

Cancer.gov

Numerous registrants have requested a certificate upon completion of the Redox Biology (RB) course. In order to obtain a certificate, you must answer 8 of the 12 questions below correctly. In the final examination, 1 question is derived from each of the 1-hour lectures. It is highly recommended that you have a copy of each PowerPoint presentation prior to taking the

Using student motivation to design groups in a non-majors biology course for team-based collaborative learning: Impacts on knowledge, views, attitudes, and perceptions

NASA Astrophysics Data System (ADS)

Walters, Kristi L.

The importance of student motivation and its connection to other learning variables (i.e., attitudes, knowledge, persistence, attendance) is well established. Collaborative work at the undergraduate level has been recognized as a valuable tool in large courses. However, motivation and collaborative group work have rarely been combined. This project utilized student motivation to learn biology to place non-major biology undergraduates in collaborative learning groups at East Carolina University, a mid-sized southeastern American university, to determine the effects of this construct on student learning. A pre-test measuring motivation to learn biology, attitudes toward biology, perceptions of biology and biologists, views of science, and content knowledge was administered. A similar post-test followed as part of the final exam. Two sections of the same introductory biology course (n = 312) were used and students were divided into homogeneous and heterogeneous groups (based on their motivation score). The heterogeneous groups (n = 32) consisted of a mixture of different motivation levels, while the homogeneous groups (n = 32) were organized into teams with similar motivation scores using tiers of high-, middle-, and low-level participants. Data analysis determined mixed perceptions of biology and biologists. These include the perceptions biology was less intriguing, less relevant, less practical, less ethical, and less understandable. Biologists were perceived as being neat and slightly intelligent, but not very altruistic, humane, ethical, logical, honest, or moral. Content knowledge scores more than doubled from pre- to post-test. Half of the items measuring views of science were not statistically significantly different from pre- to post-test. Many of the factors for attitudes toward biology became more agreeable from pre- to post-test. Correlations between motivation scores, participation levels, attendance rates, and final course grades were examined at both the individual and group level. Motivation had low correlations with the other variables. Changes in group membership (i.e., attrition) were evaluated at the group level and showed the highest rates with the heterogeneous groups and the lowest with the homogeneous middle groups. Group gender ratios were examined, but showed no correlation with final course grade. Linear regression was utilized to identify any variables that might be useful in predicting the final course grade of each student. Only participation, attendance, and final exam grade were predictive, but as they were components of the final course grade, they were not useful for the model. Differences between the groups were also examined to determine if the group type was predictive of final course grade, but no significant difference was found. Results of the study are discussed in the context of the literature on student motivation to learn science. Implications of the study are discussed through the lens of the Millennial generation's perspectives on teaching and learning. Millennials often consider an education to be a commodity and may expect results with less effort. Millennials may be expressing a pseudo-intrinsic motivation in order to impress peers and instructors, while they may actually be more extrinsically motivated to succeed

Clinical trials in progressive multiple sclerosis: lessons learned and future perspectives

PubMed Central

Ontaneda, Daniel; Fox, Robert J.; Chataway, Jeremy

2015-01-01

Progressive multiple sclerosis is characterized by the gradual accrual of disability independent of relapses and can occur with disease onset (primary progressive) or preceded by a relapsing disease course (secondary progressive). An effective disease modifying treatment for progressive multiple sclerosis has not been identified, and the results of clinical trials to date have been generally disappointing. Ongoing advances in our understanding of pathogenesis, identification of novel targets for neuro-protection, and improved outcome measures have the potential to lead to effective treatments for progressive multiple sclerosis. In this review lessons learned from previous clinical trials and perspectives from current trials in progressive multiple sclerosis are summarized. Promising clinical, imaging, and biological markers will also be reviewed, along with novel clinical trial designs. PMID:25772899

[Charles Darwin and the problem of evolutionary progress].

PubMed

Iordanskiĭ, N N

2010-01-01

According to Ch. Darwin's evolutionary theory, evolutionary progress (interpreted as morpho-physiological progress or arogenesis in recent terminology) is one of logical results of natural selection. At the same time, natural selection does not hold any factors especially promoting evolutionary progress. Darwin emphasized that the pattern of evolutionary changes depends on organism nature more than on the pattern of environment changes. Arogenesis specificity is determined by organization of rigorous biological systems - integral organisms. Onward progressive development is determined by fundamental features of living organisms: metabolism and homeostasis. The concept of social Darwinism differs fundamentally from Darwin's ideas about the most important role of social instincts in progress of mankind. Competition and selection play secondary role in socio-cultural progress of human society.

Chapter 5:Biological Properties of Wood

Treesearch

Rebecca E. Ibach

2013-01-01

There are numerous biological degradations that wood is exposed to in various environments. Biological damage occurs when a log, sawn product, or final product is not stored, handled, or designed properly. Biological organisms such as bacteria, mold, stain, decay fungi, insects, and marine borers depend heavily on temperature and moisture conditions to grow. Figure 5.1...

10 CFR 600.250 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

13 CFR 143.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

15 CFR 24.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

14 CFR 1273.50 - Closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Programs (SF-271) (as applicable). (3) Final request for payment (SF-270) (if applicable). (4) Invention... extend this timeframe. These may include but are not limited to: (1) Final performance or progress report...

Mechanisms and strategies of plant defense against Botrytis cinerea.

PubMed

AbuQamar, Synan; Moustafa, Khaled; Tran, Lam Son

2017-03-01

Biotic factors affect plant immune responses and plant resistance to pathogen infections. Despite the considerable progress made over the past two decades in manipulating genes, proteins and their levels from diverse sources, no complete genetic tolerance to environmental stresses has been developed so far in any crops. Plant defense response to pathogens, including Botrytis cinerea, is a complex biological process involving various changes at the biochemical, molecular (i.e. transcriptional) and physiological levels. Once a pathogen is detected, effective plant resistance activates signaling networks through the generation of small signaling molecules and the balance of hormonal signaling pathways to initiate defense mechanisms to the particular pathogen. Recently, studies using Arabidopsis thaliana and crop plants have shown that many genes are involved in plant responses to B. cinerea infection. In this article, we will review our current understanding of mechanisms regulating plant responses to B. cinerea with a particular interest on hormonal regulatory networks involving phytohormones salicylic acid (SA), jasmonic acid (JA), ethylene (ET) and abscisic acid (ABA). We will also highlight some potential gene targets that are promising for improving crop resistance to B. cinerea through genetic engineering and breeding programs. Finally, the role of biological control as a complementary and alternative disease management will be overviewed.

Managing, Analysing, and Integrating Big Data in Medical Bioinformatics: Open Problems and Future Perspectives

PubMed Central

Merelli, Ivan; Pérez-Sánchez, Horacio; Gesing, Sandra; D'Agostino, Daniele

2014-01-01

The explosion of the data both in the biomedical research and in the healthcare systems demands urgent solutions. In particular, the research in omics sciences is moving from a hypothesis-driven to a data-driven approach. Healthcare is additionally always asking for a tighter integration with biomedical data in order to promote personalized medicine and to provide better treatments. Efficient analysis and interpretation of Big Data opens new avenues to explore molecular biology, new questions to ask about physiological and pathological states, and new ways to answer these open issues. Such analyses lead to better understanding of diseases and development of better and personalized diagnostics and therapeutics. However, such progresses are directly related to the availability of new solutions to deal with this huge amount of information. New paradigms are needed to store and access data, for its annotation and integration and finally for inferring knowledge and making it available to researchers. Bioinformatics can be viewed as the “glue” for all these processes. A clear awareness of present high performance computing (HPC) solutions in bioinformatics, Big Data analysis paradigms for computational biology, and the issues that are still open in the biomedical and healthcare fields represent the starting point to win this challenge. PMID:25254202

GRP94/gp96 in Cancer: Biology, Structure, Immunology, and Drug Development.

PubMed

Wu, Bill X; Hong, Feng; Zhang, Yongliang; Ansa-Addo, Ephraim; Li, Zihai

2016-01-01

As an endoplasmic reticulum heat-shock protein 90 (HSP90) paralog, GRP94 (glucose-regulated protein 94)/gp96 (hereafter referred to as GRP94) has been shown to be an essential master chaperone for multiple receptors including Toll-like receptors, Wnt coreceptors, and integrins. Clinically, expression of GRP94 correlates with advanced stage and poor survival in a variety of cancers. Recent preclinical studies have also revealed that GRP94 expression is closely linked to cancer growth and metastasis in melanoma, ovarian cancer, multiple myeloma, lung cancer, and inflammation-associated colon cancer. Thus, GRP94 is an attractive therapeutic target in a number of malignancies. The chaperone function of GRP94 depends on its ATPase domain, which is structurally distinct from HSP90, allowing design of highly selective GRP94-targeted inhibitors. In this chapter, we discuss the biology and structure-function relationship of GRP94. We also summarize the immunological roles of GRP94 based on the studies documented over the last two decades, as these pertain to tumorigenesis and cancer progression. Finally, the structure-based rationale for the design of selective small-molecule inhibitors of GRP94 and their potential application in the treatment of cancer are highlighted. © 2016 Elsevier Inc. All rights reserved.

Structural, biological and biophysical properties of glycated and glycoxidized phosphatidylethanolamines

PubMed Central

Annibal, Andrea; Riemer, Thomas; Jovanovic, Olga; Westphal, Dennis; Griesser, Eva; Pohl, Elena E.; Schiller, Jürgen; Hoffmann, Ralf; Fedorova, Maria

2018-01-01

Glycation and glycoxidation of proteins and peptides have been intensively studied and are considered as reliable diagnostic biomarkers of hyperglycemia and early stages of type II diabetes. However, glucose can also react with primary amino groups present in other cellular components, such as aminophospholipids (aminoPLs). Although it is proposed that glycated aminoPLs can induce many cellular responses and contribute to the development and progression of diabetes, the routes of their formation and their biological roles are only partially revealed. The same is true for the influence of glucose-derived modifications on the biophysical properties of PLs. Here we studied structural, signaling, and biophysical properties of glycated and glycoxidized phosphatidylethanolamines (PEs). By combining high resolution mass spectrometry and nuclear magnetic resonance spectroscopy it was possible to deduce the structures of several intermediates indicating an oxidative cleavage of the Amadori product yielding glycoxidized PEs including advanced glycation end products, such as carboxyethyl- and carboxymethyl-ethanolamines. The pro-oxidative role of glycated PEs was demonstrated and further associated with several cellular responses including activation of NFκB signaling pathways. Label free proteomics indicated significant alterations in proteins regulating cellular metabolisms. Finally, the biophysical properties of PL membranes changed significantly upon PE glycation, such as melting temperature (Tm), membrane surface charge, and ion transport across the phospholipid bilayer. PMID:27012418

Extracellular matrix hydrogels from decellularized tissues: Structure and function.

PubMed

Saldin, Lindsey T; Cramer, Madeline C; Velankar, Sachin S; White, Lisa J; Badylak, Stephen F

2017-02-01

Extracellular matrix (ECM) bioscaffolds prepared from decellularized tissues have been used to facilitate constructive and functional tissue remodeling in a variety of clinical applications. The discovery that these ECM materials could be solubilized and subsequently manipulated to form hydrogels expanded their potential in vitro and in vivo utility; i.e. as culture substrates comparable to collagen or Matrigel, and as injectable materials that fill irregularly-shaped defects. The mechanisms by which ECM hydrogels direct cell behavior and influence remodeling outcomes are only partially understood, but likely include structural and biological signals retained from the native source tissue. The present review describes the utility, formation, and physical and biological characterization of ECM hydrogels. Two examples of clinical application are presented to demonstrate in vivo utility of ECM hydrogels in different organ systems. Finally, new research directions and clinical translation of ECM hydrogels are discussed. More than 70 papers have been published on extracellular matrix (ECM) hydrogels created from source tissue in almost every organ system. The present manuscript represents a review of ECM hydrogels and attempts to identify structure-function relationships that influence the tissue remodeling outcomes and gaps in the understanding thereof. There is a Phase 1 clinical trial now in progress for an ECM hydrogel. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Probabilities and predictions: modeling the development of scientific problem-solving skills.

PubMed

Stevens, Ron; Johnson, David F; Soller, Amy

2005-01-01

The IMMEX (Interactive Multi-Media Exercises) Web-based problem set platform enables the online delivery of complex, multimedia simulations, the rapid collection of student performance data, and has already been used in several genetic simulations. The next step is the use of these data to understand and improve student learning in a formative manner. This article describes the development of probabilistic models of undergraduate student problem solving in molecular genetics that detailed the spectrum of strategies students used when problem solving, and how the strategic approaches evolved with experience. The actions of 776 university sophomore biology majors from three molecular biology lecture courses were recorded and analyzed. Each of six simulations were first grouped by artificial neural network clustering to provide individual performance measures, and then sequences of these performances were probabilistically modeled by hidden Markov modeling to provide measures of progress. The models showed that students with different initial problem-solving abilities choose different strategies. Initial and final strategies varied across different sections of the same course and were not strongly correlated with other achievement measures. In contrast to previous studies, we observed no significant gender differences. We suggest that instructor interventions based on early student performances with these simulations may assist students to recognize effective and efficient problem-solving strategies and enhance learning.

Using Genetically Engineered Animal Models in the Postgenomic Era to Understand Gene Function in Alcoholism

PubMed Central

Reilly, Matthew T.; Harris, R. Adron; Noronha, Antonio

2012-01-01

Over the last 50 years, researchers have made substantial progress in identifying genetic variations that underlie the complex phenotype of alcoholism. Not much is known, however, about how this genetic variation translates into altered biological function. Genetic animal models recapitulating specific characteristics of the human condition have helped elucidate gene function and the genetic basis of disease. In particular, major advances have come from the ability to manipulate genes through a variety of genetic technologies that provide an unprecedented capacity to determine gene function in the living organism and in alcohol-related behaviors. Even newer genetic-engineering technologies have given researchers the ability to control when and where a specific gene or mutation is activated or deleted, allowing investigators to narrow the role of the gene’s function to circumscribed neural pathways and across development. These technologies are important for all areas of neuroscience, and several public and private initiatives are making a new generation of genetic-engineering tools available to the scientific community at large. Finally, high-throughput “next-generation sequencing” technologies are set to rapidly increase knowledge of the genome, epigenome, and transcriptome, which, combined with genetically engineered mouse mutants, will enhance insight into biological function. All of these resources will provide deeper insight into the genetic basis of alcoholism. PMID:23134044

Using genetically engineered animal models in the postgenomic era to understand gene function in alcoholism.

PubMed

Reilly, Matthew T; Harris, R Adron; Noronha, Antonio

2012-01-01

Over the last 50 years, researchers have made substantial progress in identifying genetic variations that underlie the complex phenotype of alcoholism. Not much is known, however, about how this genetic variation translates into altered biological function. Genetic animal models recapitulating specific characteristics of the human condition have helped elucidate gene function and the genetic basis of disease. In particular, major advances have come from the ability to manipulate genes through a variety of genetic technologies that provide an unprecedented capacity to determine gene function in the living organism and in alcohol-related behaviors. Even newer genetic-engineering technologies have given researchers the ability to control when and where a specific gene or mutation is activated or deleted, allowing investigators to narrow the role of the gene's function to circumscribed neural pathways and across development. These technologies are important for all areas of neuroscience, and several public and private initiatives are making a new generation of genetic-engineering tools available to the scientific community at large. Finally, high-throughput "next-generation sequencing" technologies are set to rapidly increase knowledge of the genome, epigenome, and transcriptome, which, combined with genetically engineered mouse mutants, will enhance insight into biological function. All of these resources will provide deeper insight into the genetic basis of alcoholism.

1999 Gordon Research Conference on Mammalian DNA Repair. Final Progress Report

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

NONE

1999-02-12

This Conference will examine DNA repair as the key component in genomic surveillance that is so crucial to the overall integrity and function of mammalian cells. Recent discoveries have catapulted the field of DNA repair into a pivotal position for fundamental investigations into oncology, aging, environmental health, and developmental biology. We hope to highlight the most promising and exciting avenues of research in robust discussions at this conference. This Mammalian DNA Repair Gordon Conference differs from the past conferences in this series, in which the programs were broader in scope, with respect to topics and biological systems covered. A conferencemore » sponsored by the Genetics Society in April 1998 emphasized recombinational mechanisms for double-strand break repair and the role of mismatch repair deficiency in colorectal cancer. These topics will therefore receive somewhat less emphasis in the upcoming Conference. In view of the recent mechanistic advances in mammalian DNA repair, an upcoming comprehensive DNA repair meeting next autumn at Hilton Head; and the limited enrollment for Gordon Conferences we have decided to focus session-by-session on particular areas of controversy and/or new developments specifically in mammalian systems. Thus, the principal presentations will draw upon results from other cellular systems only to the extent that they impact our understanding of mammalian DNA repair.« less

The interplay of biology and technology

PubMed Central

Fields, Stanley

2001-01-01

Technologies for biological research arise in multiple ways—through serendipity, through inspired insights, and through incremental advances—and they are tightly coupled to progress in engineering. Underlying the complex dynamics of technology and biology are the different motivations of those who work in the two realms. Consideration of how methodologies emerge has implications for the planning of interdisciplinary centers and the training of the next generation of scientists. PMID:11517346

Integrating biological redesign: where synthetic biology came from and where it needs to go.

PubMed

Way, Jeffrey C; Collins, James J; Keasling, Jay D; Silver, Pamela A

2014-03-27

Synthetic biology seeks to extend approaches from engineering and computation to redesign of biology, with goals such as generating new chemicals, improving human health, and addressing environmental issues. Early on, several guiding principles of synthetic biology were articulated, including design according to specification, separation of design from fabrication, use of standardized biological parts and organisms, and abstraction. We review the utility of these principles over the past decade in light of the field's accomplishments in building complex systems based on microbial transcription and metabolism and describe the progress in mammalian cell engineering. Copyright © 2014 Elsevier Inc. All rights reserved.

Downregulation of the expression of HDGF attenuates malignant biological behaviors of hilar cholangiocarcinoma cells.

PubMed

Liu, Yanfeng; Sun, Jingxian; Yang, Guangyun; Liu, Zhaojian; Guo, Sen; Zhao, Rui; Xu, Kesen; Wu, Xiaopeng; Zhang, Zhaoyang

2015-09-01

Hepatoma-derived growth factor (HDGF) has been reported to be a potential predictive and prognostic marker for several types of cancer and important in malignant biological behaviors. However, its role in human hilar cholangiocarcinoma remains to be elucidated. Our previous study demonstrated that high expression levels of HDGF in hilar cholangiocarcinoma tissues correlates with tumor progression and patient outcome. The present study aimed to elucidate the detailed functions of the HDGF protein. This was performed by downregulating the protein expression of HDGF in the FRH0201 hilar cholangiocarcinoma cell line by RNA interference (RNAi) in vitro, and revealed that downregulation of the HDGF protein significantly inhibited the malignant biological behavior of the FRH0201 cells. In addition, further investigation revealed that downregulation of the protein expression of HDGF significantly decreased the secretion of vascular endothelial growth factor, which may be the mechanism partially responsible for the inhibition of malignant biological behaviors. These findings demonstrated that HDGF is important in promoting malignant biological behaviors, including proliferation, migration and invasion of hilar cholangiocarcinoma FRH0201 cells. Inhibition of the expression of HDGF downregulated the malignant biological behaviors, suggesting that downregulation of the protein expression of HDGF by RNAi may be a novel therapeutic approach to inhibit the progression of hilar cholangiocarcinoma.

Excellence in the Classroom

ERIC Educational Resources Information Center

Governor's Business Council (Texas), 2006

2006-01-01

Texas has made good progress in education since the school reform movement began in earnest 15 years ago. State test scores are up for all groups of students in all grades in all subjects. On the National Assessment of Educational Progress, Texas is close to the top in student performance in math, and has finally begun to make real progress in…

Biology, Medicine, and the Bill of Rights. Special Report.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Office of Technology Assessment.

The rapid progress in the biological sciences has resulted in many social, ethical, and legal issues. In medical practice, public health programs, research laboratories, law enforcement, insurance, the patenting process, agriculture, genetic counseling, and other fields, legal controversies and public policy debates have developed. Some of these…

Biological and medical research with accelerated heavy ions at the Bevalac, 1977-1980. [Lead abstract

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

Pirruccello, M.C.; Tobias, C.A.

1980-11-01

Separate abstracts were prepared for the 46 papers presented in this progress report. This report is a major review of studies with accelerated heavy ions carried out by the Biology and Medicine Division of Lawrence Berkeley Laboratory from 1977 to 1980. (KRM)

PREDICTING LEVELS OF STRESS FROM BIOLOGICAL ASSESSMENT DATA: EMPIRICAL MODELS FROM THE EASTERN CORN BELT PLAINS

EPA Science Inventory

Biological assessment is becoming an increasingly popular tool in the evaluation of stream ecosystem integrity. However, little progress has been made to date in developing tools to relate assessment results to specific stressors. This paper continues the investigation of the f...

Recent progress in a classical biological control program for olive fruit fly in California

USDA-ARS?s Scientific Manuscript database

The olive fruit fly, Bactrocera oleae (Diptera: Tephritidae), causes severe damage to olive production worldwide. Control of olive fruit fly typically relies on pesticides, and under such conditions the impact of natural enemies is relatively low. About 15 years ago, the USDA-ARS European Biologic...

Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development.

PubMed

Andersen, Morten; Sajid, Zamra; Pedersen, Rasmus K; Gudmand-Hoeyer, Johanne; Ellervik, Christina; Skov, Vibe; Kjær, Lasse; Pallisgaard, Niels; Kruse, Torben A; Thomassen, Mads; Troelsen, Jesper; Hasselbalch, Hans Carl; Ottesen, Johnny T

2017-01-01

The chronic Philadelphia-negative myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms which ultimately may transform to acute myelogenous leukemia. Most recently, chronic inflammation has been described as an important factor for the development and progression of MPNs in the biological continuum from early cancer stage to the advanced myelofibrosis stage, the MPNs being described as "A Human Inflammation Model for Cancer Development". This novel concept has been built upon clinical, experimental, genomic, immunological and not least epidemiological studies. Only a few studies have described the development of MPNs by mathematical models, and none have addressed the role of inflammation for clonal evolution and disease progression. Herein, we aim at using mathematical modelling to substantiate the concept of chronic inflammation as an important trigger and driver of MPNs.The basics of the model describe the proliferation from stem cells to mature cells including mutations of healthy stem cells to become malignant stem cells. We include a simple inflammatory coupling coping with cell death and affecting the basic model beneath. First, we describe the system without feedbacks or regulatory interactions. Next, we introduce inflammatory feedback into the system. Finally, we include other feedbacks and regulatory interactions forming the inflammatory-MPN model. Using mathematical modeling, we add further proof to the concept that chronic inflammation may be both a trigger of clonal evolution and an important driving force for MPN disease progression. Our findings support intervention at the earliest stage of cancer development to target the malignant clone and dampen concomitant inflammation.

Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

PubMed Central

Ford, Catriona A.; Petrova, Sofia; Pound, John D.; Voss, Jorine J.L.P.; Melville, Lynsey; Paterson, Margaret; Farnworth, Sarah L.; Gallimore, Awen M.; Cuff, Simone; Wheadon, Helen; Dobbin, Edwina; Ogden, Carol Anne; Dumitriu, Ingrid E.; Dunbar, Donald R.; Murray, Paul G.; Ruckerl, Dominik; Allen, Judith E.; Hume, David A.; van Rooijen, Nico; Goodlad, John R.; Freeman, Tom C.; Gregory, Christopher D.

2015-01-01

Summary Background Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Results Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. Conclusions In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. PMID:25702581

Psychosocial influences on HIV-1 disease progression: neural, endocrine, and virologic mechanisms.

PubMed

Cole, Steve W

2008-06-01

This review surveys empirical research pertinent to the hypothesis that activity of the hypothalamus-pituitary-adrenal (HPA) axis and/or the sympathetic nervous system (SNS) might mediate biobehavioral influences on HIV-1 pathogenesis and disease progression. Data are considered based on causal effects of neuroeffector molecules on HIV-1 replication, prospective relationships between neural/endocrine parameters and HIV-relevant biological or clinical markers, and correlational data consistent with in vivo neural/endocrine mediation in human or animal studies. Results show that HPA and SNS effector molecules can enhance HIV-1 replication in cellular models via effects on viral infectivity, viral gene expression, and the innate immune response to infection. Animal models and human clinical studies both provide evidence consistent with SNS regulation of viral replication, but data on HPA mediation are less clear. Regulation of leukocyte biology by neuroeffector molecules provides a plausible biological mechanism by which psychosocial factors might influence HIV-1 pathogenesis, even in the era of effective antiretroviral therapy. As such, neural and endocrine parameters might provide useful biomarkers for gauging the promise of behavioral interventions and suggest novel adjunctive strategies for controlling HIV-1 disease progression.

Network biology: Describing biological systems by complex networks. Comment on "Network science of biological systems at different scales: A review" by M. Gosak et al.

NASA Astrophysics Data System (ADS)

Jalili, Mahdi

2018-03-01

I enjoyed reading Gosak et al. review on analysing biological systems from network science perspective [1]. Network science, first started within Physics community, is now a mature multidisciplinary field of science with many applications ranging from Ecology to biology, medicine, social sciences, engineering and computer science. Gosak et al. discussed how biological systems can be modelled and described by complex network theory which is an important application of network science. Although there has been considerable progress in network biology over the past two decades, this is just the beginning and network science has a great deal to offer to biology and medical sciences.

Grand challenges in space synthetic biology

PubMed Central

Montague, Michael G.; Cumbers, John; Hogan, John A.

2015-01-01

Space synthetic biology is a branch of biotechnology dedicated to engineering biological systems for space exploration, industry and science. There is significant public and private interest in designing robust and reliable organisms that can assist on long-duration astronaut missions. Recent work has also demonstrated that such synthetic biology is a feasible payload minimization and life support approach as well. This article identifies the challenges and opportunities that lie ahead in the field of space synthetic biology, while highlighting relevant progress. It also outlines anticipated broader benefits from this field, because space engineering advances will drive technological innovation on Earth. PMID:26631337

Analyzing Data for Systems Biology: Working at the Intersection of Thermodynamics and Data Analytics

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

Cannon, William R.; Baxter, Douglas J.

2012-08-15

Many challenges in systems biology have to do with analyzing data within the framework of molecular phenomena and cellular pathways. How does this relate to thermodynamics that we know govern the behavior of molecules? Making progress in relating data analysis to thermodynamics is essential in systems biology if we are to build predictive models that enable the field of synthetic biology. This report discusses work at the crossroads of thermodynamics and data analysis, and demonstrates that statistical mechanical free energy is a multinomial log likelihood. Applications to systems biology are presented.

Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost-effectiveness analysis.

PubMed

Finckh, Axel; Bansback, Nick; Marra, Carlo A; Anis, Aslam H; Michaud, Kaleb; Lubin, Stanley; White, Marc; Sizto, Sonia; Liang, Matthew H

2009-11-03

Long-term control or remission of rheumatoid arthritis (RA) may be possible with very early treatment. However, no optimal first therapeutic strategy has been determined. To assess the potential cost-effectiveness of major therapeutic strategies for very early RA. Decision analytic model with probabilistic sensitivity analyses. Published data, the National Data Bank for Rheumatic Diseases, and actual 2007 hospital costs. U.S. adults with very early RA (symptom duration

Spontaneous regression of curve in immature idiopathic scoliosis - does spinal column play a role to balance? An observation with literature review.

PubMed

Modi, Hitesh N; Suh, Seung-Woo; Yang, Jae-Hyuk; Hong, Jae-Young; Venkatesh, Kp; Muzaffar, Nasir

2010-11-04

Child with mild scoliosis is always a subject of interest for most orthopaedic surgeons regarding progression. Literature described Hueter-Volkmann theory regarding disc and vertebral wedging, and muscular imbalance for the progression of adolescent idiopathic scoliosis. However, many authors reported spontaneous resolution of curves also without any reason for that and the rate of resolution reported is almost 25%. Purpose of this study was to question the role of paraspinal muscle tuning/balancing mechanism, especially in patients with idiopathic scoliosis with early mild curve, for spontaneous regression or progression as well as changing pattern of curves. An observational study of serial radiograms in 169 idiopathic scoliosis children (with minimum follow-up one year) was carried. All children with Cobb angle < 25° and who were diagnosed for the first time were selected. As a sign of immaturity at the time of diagnosis, all children had Risser sign 0. No treatment was given to entire study group. Children were divided in three groups at final follow-up: Group A, B and C as children with regression, no change and progression of their curves, respectively. Additionally changes in the pattern of curve were also noted. Average age was 9.2 years at first visit and 10.11 years at final follow-up with an average follow-up of 21 months. 32.5% (55/169), 41.4% (70/169) and 26% (44/169) children exhibited regression, no change and progression in their curves, respectively. 46.1% of children (78/169) showed changing pattern of their curves during the follow-up visits before it settled down to final curve. Comparing final fate of curve with side of curve and number of curves it did not show any relationship (p > 0.05) in our study population. Possible reason for changing patterns could be better explained by the tuning/balancing mechanism of spinal column that makes an effort to balance the spine and result into spontaneous regression or prevent further progression of curve. If this which we called as "tuning/balancing mechanism" fails, curve will ultimately progress.

Potential control of multiple sclerosis by cannabis and the endocannabinoid system.

PubMed

Pryce, Gareth; Baker, David

2012-08-01

For many years, multiple sclerosis (MS) patients have been self-medicating with illegal street cannabis to alleviate symptoms associated with MS. Data from animal models of MS and clinical studies have supported the anecdotal data that cannabis can improve symptoms such as limb spasticity, which are commonly associated with progressive MS, by the modulation of excessive neuronal signalling. This has lead to cannabis-based medicines being approved for the treatment of pain and spasticity in MS for the first time. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have activity, not only in symptom relief but also potentially in neuroprotective strategies which may slow disease progression and thus delay the onset of symptoms such as spasticity. This review appraises the current knowledge of cannabinoid biology particularly as it pertains to MS and outlines potential future therapeutic strategies for the treatment of disease progression in MS.

Short communication: Characteristics of student success in an undergraduate physiology and anatomy course.

PubMed

Gwazdauskas, F C; McGilliard, M L; Corl, B A

2014-10-01

Several factors affect the success of students in college classes. The objective of this research was to determine what factors affect success of undergraduate students in an anatomy and physiology class. Data were collected from 602 students enrolled in the Agriculture and Life Sciences (ALS) 2304 Animal Physiology and Anatomy course from 2005 through 2012. The data set included 476 females (79.1%) and 126 males (20.9%). Time to complete exams was recorded for each student. For statistical analyses, students' majors were animal and poultry sciences (APSC), agricultural sciences, biochemistry, biological sciences, dairy science, and "other," which combined all other majors. All analyses were completed using the GLIMMIX procedure of SAS (SAS Institute Inc., Cary, NC). Gender, major, matriculation year, major by year interaction, gender by year interaction, and time to complete the exam affected final course grade. The significant gender effect was manifested in the final grade percentage of 75.9 ± 0.4 for female students compared with 72.3 ± 0.6 for male students. Junior males had final course grades comparable with those of females, but sophomore and senior males had lower final course grades than other combinations. Biology majors had a final grade of 82.4 ± 0.6 and this grade was greater than all other majors. Students classified as "other" had a final score of 74.4 ± 0.8, which was greater than agricultural science majors (69.5 ± 0.9). The APSC grade (72.6 ± 0.5) was higher than the agricultural science majors. Junior students had significantly greater final grades (76.1 ± 0.5) than sophomores (73.3 ± 0.6) and seniors (72.9 ± 0.9). All biology students had greater final grades than all other majors, but biochemistry juniors had greater final course grades than APSC, agricultural science, and dairy science juniors. "Other" seniors had greater final course grades than agricultural science seniors. The regression for time to complete the exam was curvilinear and suggests that highest exam scores were at about 90-min completion time. It may be that some male students need better preparation for anatomy and physiology and their educational preparation should mimic that of female students more in terms of advance-placement biology in high school. These results suggest that biology majors might be better prepared for animal anatomy and physiology than other students. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Evolving Relevance of Neuroproteomics in Alzheimer's Disease.

PubMed

Lista, Simone; Zetterberg, Henrik; O'Bryant, Sid E; Blennow, Kaj; Hampel, Harald

2017-01-01

Substantial progress in the understanding of the biology of Alzheimer's disease (AD) has been achieved over the past decades. The early detection and diagnosis of AD and other age-related neurodegenerative diseases, however, remain a challenging scientific frontier. Therefore, the comprehensive discovery (relating to all individual, converging or diverging biochemical disease mechanisms), development, validation, and qualification of standardized biological markers with diagnostic and prognostic functions with a precise performance profile regarding specificity, sensitivity, and positive and negative predictive value are warranted.Methodological innovations in the area of exploratory high-throughput technologies, such as sequencing, microarrays, and mass spectrometry-based analyses of proteins/peptides, have led to the generation of large global molecular datasets from a multiplicity of biological systems, such as biological fluids, cells, tissues, and organs. Such methodological progress has shifted the attention to the execution of hypothesis-independent comprehensive exploratory analyses (opposed to the classical hypothesis-driven candidate approach), with the aim of fully understanding the biological systems in physiology and disease as a whole. The systems biology paradigm integrates experimental biology with accurate and rigorous computational modelling to describe and foresee the dynamic features of biological systems. The use of dynamically evolving technological platforms, including mass spectrometry, in the area of proteomics has enabled to rush the process of biomarker discovery and validation for refining significantly the diagnosis of AD. Currently, proteomics-which is part of the systems biology paradigm-is designated as one of the dominant matured sciences needed for the effective exploratory discovery of prospective biomarker candidates expected to play an effective role in aiding the early detection, diagnosis, prognosis, and therapy development in AD.

Tough Acts to Follow: The Challenges to Science Teachers Presented by Biotechnological Progress

ERIC Educational Resources Information Center

Bryce, Tom; Gray, Donald

2004-01-01

The public controversies associated with biotechnological progress (genetic modification, cloning, and so forth) increasingly impact upon biology teaching in school; teachers find themselves engaged in discussions with pupils on value-laden issues deriving from the social and ethical implications of the 'new science'. The research described in…

Driving Discovery | Division of Cancer Prevention

Cancer.gov

Progress against cancer depends on many types of research—including basic, translational, and clinical—across different research areas, from the biology of cancer cells to studies of large populations. Regardless of the research type or area, supporting the best science and the best scientists is of paramount importance to NCI. Learn more about driving progress against cancer.

Challenges and progress in distributed watershed modeling: applications of the AgroEcoSystem-Watershed (AgES-W) model

USDA-ARS?s Scientific Manuscript database

Progress in the understanding of physical, chemical, and biological processes influencing water quality, coupled with advances in the collection and analysis of hydrologic data, provide opportunities for significant innovations in the manner and level with which watershed-scale processes may be quan...

The TICKING of the Biological and Tenure Clocks

ERIC Educational Resources Information Center

Valdata, Patricia

2005-01-01

Colleges and universities are arguably among the most enlightened and progressive institutions in America. So when it comes to maternity and career policies, one would expect that they would be at the forefront of similarly progressive accommodation practices. But in fact, colleges and universities have only recently begun to address this issue.…

A "Vision and Change" Reform of Introductory Biology Shifts Faculty Perceptions and Use of Active Learning

ERIC Educational Resources Information Center

Auerbach, Anna Jo; Schussler, Elisabeth

2017-01-01

Increasing faculty use of active-learning (AL) pedagogies in college classrooms is a persistent challenge in biology education. A large research-intensive university implemented changes to its biology majors' two-course introductory sequence as outlined by the "Vision and Change in Undergraduate Biology Education" final report. One goal…

40 CFR 60.2575 - What are my requirements for meeting increments of progress and achieving final compliance?

Code of Federal Regulations, 2012 CFR

2012-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY... Units Model Rule-Increments of Progress § 60.2575 What are my requirements for meeting increments of...

40 CFR 60.2575 - What are my requirements for meeting increments of progress and achieving final compliance?

Code of Federal Regulations, 2014 CFR

2014-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY... Units Model Rule-Increments of Progress § 60.2575 What are my requirements for meeting increments of...

40 CFR 60.2575 - What are my requirements for meeting increments of progress and achieving final compliance?

Code of Federal Regulations, 2013 CFR

2013-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY... Units Model Rule-Increments of Progress § 60.2575 What are my requirements for meeting increments of...

New genes contribute to genetic and phenotypic novelties in human evolution

PubMed Central

Zhang, Yong E.; Long, Manyuan

2014-01-01

New genes in human genomes have been found relevant in evolution and biology of humans. It was conservatively estimated that the human genome encodes more than 300 human-specific genes and 1,000 primate-specific genes. These new arrivals appear to be implicated in brain function and male reproduction. Surprisingly, increasing evidence indicates that they may also bring negative pleiotropic effects, while assuming various possible biological functions as sources of phenotypic novelties, suggesting a non-progressive route for functional evolution. Similar to these fixed new genes, polymorphic new genes were found to contribute to functional evolution within species, e.g. with respect to digestion or disease resistance, revealing that new genes can acquire new or diverged functions in its initial stage as prototypic genes. These progresses have provided new opportunity to explore the genetic basis of human biology and human evolutionary history in a new dimension. PMID:25218862

Technological advances in precision medicine and drug development.

PubMed

Maggi, Elaine; Patterson, Nicole E; Montagna, Cristina

New technologies are rapidly becoming available to expand the arsenal of tools accessible for precision medicine and to support the development of new therapeutics. Advances in liquid biopsies, which analyze cells, DNA, RNA, proteins, or vesicles isolated from the blood, have gained particular interest for their uses in acquiring information reflecting the biology of tumors and metastatic tissues. Through advancements in DNA sequencing that have merged unprecedented accuracy with affordable cost, personalized treatments based on genetic variations are becoming a real possibility. Extraordinary progress has been achieved in the development of biological therapies aimed to even further advance personalized treatments. We provide a summary of current and future applications of blood based liquid biopsies and how new technologies are utilized for the development of biological therapeutic treatments. We discuss current and future sequencing methods with an emphasis on how technological advances will support the progress in the field of precision medicine.

Systems Proteomics for Translational Network Medicine

PubMed Central

Arrell, D. Kent; Terzic, Andre

2012-01-01

Universal principles underlying network science, and their ever-increasing applications in biomedicine, underscore the unprecedented capacity of systems biology based strategies to synthesize and resolve massive high throughput generated datasets. Enabling previously unattainable comprehension of biological complexity, systems approaches have accelerated progress in elucidating disease prediction, progression, and outcome. Applied to the spectrum of states spanning health and disease, network proteomics establishes a collation, integration, and prioritization algorithm to guide mapping and decoding of proteome landscapes from large-scale raw data. Providing unparalleled deconvolution of protein lists into global interactomes, integrative systems proteomics enables objective, multi-modal interpretation at molecular, pathway, and network scales, merging individual molecular components, their plurality of interactions, and functional contributions for systems comprehension. As such, network systems approaches are increasingly exploited for objective interpretation of cardiovascular proteomics studies. Here, we highlight network systems proteomic analysis pipelines for integration and biological interpretation through protein cartography, ontological categorization, pathway and functional enrichment and complex network analysis. PMID:22896016

Oxidative stress and adipocyte biology: focus on the role of AGEs.

PubMed

Boyer, Florence; Vidot, Jennifer Baraka; Dubourg, Alexis Guerin; Rondeau, Philippe; Essop, M Faadiel; Bourdon, Emmanuel

2015-01-01

Diabetes is a major health problem that is usually associated with obesity, together with hyperglycemia and increased advanced glycation endproducts (AGEs) formation. Elevated AGEs elicit severe downstream consequences via their binding to receptors of AGEs (RAGE). This includes oxidative stress and oxidative modifications of biological compounds together with heightened inflammation. For example, albumin (major circulating protein) undergoes increased glycoxidation with diabetes and may represent an important biomarker for monitoring diabetic pathophysiology. Despite the central role of adipose tissue in many physiologic/pathologic processes, recognition of the effects of greater AGEs formation in this tissue is quite recent within the obesity/diabetes context. This review provides a brief background of AGEs formation and adipose tissue biology and thereafter discusses the impact of AGEs-adipocyte interactions in pathology progression. Novel data are included showing how AGEs (especially glycated albumin) may be involved in hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression.

DiME: A Scalable Disease Module Identification Algorithm with Application to Glioma Progression

PubMed Central

Liu, Yunpeng; Tennant, Daniel A.; Zhu, Zexuan; Heath, John K.; Yao, Xin; He, Shan

2014-01-01

Disease module is a group of molecular components that interact intensively in the disease specific biological network. Since the connectivity and activity of disease modules may shed light on the molecular mechanisms of pathogenesis and disease progression, their identification becomes one of the most important challenges in network medicine, an emerging paradigm to study complex human disease. This paper proposes a novel algorithm, DiME (Disease Module Extraction), to identify putative disease modules from biological networks. We have developed novel heuristics to optimise Community Extraction, a module criterion originally proposed for social network analysis, to extract topological core modules from biological networks as putative disease modules. In addition, we have incorporated a statistical significance measure, B-score, to evaluate the quality of extracted modules. As an application to complex diseases, we have employed DiME to investigate the molecular mechanisms that underpin the progression of glioma, the most common type of brain tumour. We have built low (grade II) - and high (GBM) - grade glioma co-expression networks from three independent datasets and then applied DiME to extract potential disease modules from both networks for comparison. Examination of the interconnectivity of the identified modules have revealed changes in topology and module activity (expression) between low- and high- grade tumours, which are characteristic of the major shifts in the constitution and physiology of tumour cells during glioma progression. Our results suggest that transcription factors E2F4, AR and ETS1 are potential key regulators in tumour progression. Our DiME compiled software, R/C++ source code, sample data and a tutorial are available at http://www.cs.bham.ac.uk/~szh/DiME. PMID:24523864

The versatile role of exosomes in cancer progression: diagnostic and therapeutic implications.

PubMed

Sundararajan, Vignesh; Sarkar, Fazlul H; Ramasamy, Thamil Selvee

2018-06-01

Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming. While exosomes interact with cells within the tumour microenvironment to promote tumour growth, these vesicles can also facilitate the process of distant metastasis by mediating the formation of pre-metastatic niches. Next to their tumour promoting effects, exosomes have been found to serve as potential tools for cancer diagnosis and therapy. The ease of isolating exosomes and their content from different body fluids has led to the identification of diagnostic and prognostic biomarker signatures, as well as to predictive biomarker signatures for therapeutic responses. Exosomes can also be used as cargos to deliver therapeutic anti-cancer drugs, and they can be engineered to serve as vaccines for immunotherapy. Additionally, it has been found that inhibition of exosome secretion, and thus the transfer of oncogenic molecules, holds promise for inhibiting tumour growth. Here we provide recent information on the diverse roles of exosomes in various cellular and systemic processes governing cancer progression, and discuss novel strategies to halt this progression using exosome-based targeted therapies and methods to inhibit exosome secretion and the transfer of pro-tumorigenic molecules. This review highlights the important role of exosomes in cancer progression and its implications for (non-invasive) diagnostics and the development of novel therapeutic strategies, as well as its current and future applications in clinical trials.

ECOLOGICAL IMPACT OF INTEGRATED CHEMICAL AND BIOLOGICAL AQUATIC WEED CONTROL

EPA Science Inventory

This final report presents results of a four-year study of the ecological impacts of chemical, biological, and integrated methods of aquatic weed control. Biological and water quality changes occurred as abundance of macrophytic vegetation was altered by natural factors or manage...

Traditional schemes for treatment of psoriatic arthritis.

PubMed

McHugh, Neil J

2009-08-01

Prior to the availability of biologic agents such as anti-tumor necrosis factor (TNF), traditional treatment schemes for psoriatic arthritis were not extensively evaluated. While it appears that the newer forms of treatment are more effective, conventional agents still need to be scrutinized with similar methodology and will still have a role in those patients with less progressive disease, in combination with biologic agents, and in patients where biologics are not tolerated or have failed.

FINAL Progress Report DOE Grant DE-FG02-04ER15587

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

Mullins, Charles Buddie

Catalysis Program - Viviane Schwartz Program Manager This Final Report discusses several archival journal articles that have been published that present and discuss the results that were discovered through this DOE grant.

78 FR 60226 - Amendments To Implement Certain Provisions of the Moving Ahead for Progress in the 21st Century...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

... Moving Ahead for Progress in the 21st Century Act (MAP-21) AGENCY: Federal Motor Carrier Safety...) adopts, as final, certain regulations required by the Moving Ahead for Progress in the 21st Century... required by MAP-21. Benefits and Costs The rule provisions considered both individually and in the...

Making Progress: The Use of Multiple Progress Reports to Enhance Advertising Students' Media Plan Term Projects

ERIC Educational Resources Information Center

Kritz, Gary H.; Lozada, Hector R.; Long, Mary M.

2007-01-01

Since the AACSB mandates that students demonstrate effective oral and written communication skills, it is imperative that business professors do what is necessary to improve such skills. The authors investigate whether the use of using multiple progress reports in an Advertising class project improves the final product. The data results show that…

78 FR 65705 - Request for Comments on the Annual Progress Report on the Outer Continental Shelf (OCS) Oil and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... (Five Year Program). The Annual Progress Report is available for review at: www.boem.gov/Five-Year-Program-Annual-Progress-Report/ . Information on the Five Year Program is available online at http://www... final on August 27, 2012, after the required 60-day congressional review period. Section 18(e) of the...

Gender Differences and Styles in the Use of Digital Games

ERIC Educational Resources Information Center

Bonanno, Philip; Kommers, P. A. M.

2005-01-01

This paper reports work in progress investigating gender differences and styles in the use of digital games amongst advanced level biology students. It is an elaboration on previous work exploring the relationship between cognitive style and academic performance in Maltese students taking biology at advanced level. In this previous work the…

Hybridization between a native and introduced predator of Adelgidae: An unintended result of classical biological control

Treesearch

N.P. Havill; Gina Davis; David Mausel; Joanne Klein; Richard McDonald; Cera Jones; Melissa Fischer; Scott Salom; Adelgisa Caccone

2012-01-01

Hybridization between introduced biological control agents and native species has the potential to impact native biodiversity and pest control efforts. This study reports progress towards predicting the outcome of hybridization between two beetle species, the introduced Laricobius nigrinus Fender and the native L. rubidus LeConte...

Barrett's Esophagus Translational Research Network (BETRNet) | Division of Cancer Prevention

Cancer.gov

The goal of BETRNet is to reduce the incidence, morbidity, and mortality of esophageal adenocarcinoma by answering key questions related to the progression of the disease, especially in the premalignant stage. In partnership with NCI’s Division of Cancer Biology, multidisciplinary translational research centers collaborate to better understand the biology of Barrett's

Biomimetic robots using EAP as artificial muscles - progress and challenges

NASA Technical Reports Server (NTRS)

Bar-Cohen, Yoseph

2004-01-01

Biology offers a great model for emulation in areas ranging from tools, computational algorithms, materials science, mechanisms and information technology. In recent years, the field of biomimetics, namely mimicking biology, has blossomed with significant advances enabling the reverse engineering of many animals' functions and implementation of some of these capabilities.

Comparative genetics: a lens through which to clarify the genomes, the transmission history, and the reproductive biology of Trichinella spp.

USDA-ARS?s Scientific Manuscript database

Progress in studying the biology of Trichinella spp. was greatly advanced with the publication and analysis of the draft genome sequence of T. spiralis. Those data provide a basis for constructing testable hypothesis concerning parasite physiology, immunology, and genetics. They also provide tools...

'Biologic memory' in response to acute kidney injury: cytoresistance, toll-like receptor hyper-responsiveness and the onset of progressive renal disease.

PubMed

Zager, Richard A

2013-08-01

Following the induction of ischemic or toxin-mediated acute kidney injury (AKI), cellular adaptations occur that 're-program' how the kidney responds to future superimposed insults. This re-programming is not simply a short-lived phenomenon; rather it can persist for many weeks, implying that a state of 'biologic memory' has emerged. These changes can be both adaptive and maladaptive in nature and they can co-exist in time. A beneficial adaptation is the emergence of acquired cytoresistance, whereby a number of physiologic responses develop that serve to protect the kidney against further ischemic or nephrotoxic attack. Conversely, some changes are maladaptive, such as a predisposition to Gram-negative or Gram-positive bacteremia due to a renal tubular up-regulation of toll-like receptor responses. This latter change culminates in exaggerated cytokine production, and with efflux into the systemic circulation, extra-renal tissue injury can result (so-called 'organ cross talk'). Another maladaptive response is a persistent up-regulation of pro-inflammatory, pro-fibrotic and vasoconstrictive genes, culminating in progressive renal injury and ultimately end-stage renal failure. The mechanisms by which this biologic re-programming, or biologic memory, is imparted remain subjects for considerable debate. However, injury-induced, and stable, epigenetic remodeling at pro-inflammatory/pro-fibrotic genes seems likely to be involved. The goal of this editorial is to highlight that the so-called 'maintenance phase' of acute renal failure is not a static one, somewhere between injury induction and the onset of repair. Rather, this period is one in which the induction of 'biologic memory' can ultimately impact renal functional recovery, extra-renal injury and the possible transition of AKI into chronic, progressive renal disease.

Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression.

PubMed

Willms, Eduard; Cabañas, Carlos; Mäger, Imre; Wood, Matthew J A; Vader, Pieter

2018-01-01

Cells release membrane enclosed nano-sized vesicles termed extracellular vesicles (EVs) that function as mediators of intercellular communication by transferring biological information between cells. Tumor-derived EVs have emerged as important mediators in cancer development and progression, mainly through transfer of their bioactive content which can include oncoproteins, oncogenes, chemokine receptors, as well as soluble factors, transcripts of proteins and miRNAs involved in angiogenesis or inflammation. This transfer has been shown to influence the metastatic behavior of primary tumors. Moreover, tumor-derived EVs have been shown to influence distant cellular niches, establishing favorable microenvironments that support growth of disseminated cancer cells upon their arrival at these pre-metastatic niches. It is generally accepted that cells release a number of major EV populations with distinct biophysical properties and biological functions. Exosomes, microvesicles, and apoptotic bodies are EV populations most widely studied and characterized. They are discriminated based primarily on their intracellular origin. However, increasing evidence suggests that even within these EV populations various subpopulations may exist. This heterogeneity introduces an extra level of complexity in the study of EV biology and function. For example, EV subpopulations could have unique roles in the intricate biological processes underlying cancer biology. Here, we discuss current knowledge regarding the role of subpopulations of EVs in cancer development and progression and highlight the relevance of EV heterogeneity. The position of tetraspanins and integrins therein will be highlighted. Since addressing EV heterogeneity has become essential for the EV field, current and novel techniques for isolating EV subpopulations will also be discussed. Further dissection of EV heterogeneity will advance our understanding of the critical roles of EVs in health and disease.

Multi-walled carbon nanotubes and metallic nanoparticles and their application in biomedicine.

PubMed

Rojas-Chapana, Jose A; Giersig, Michael

2006-02-01

Interdisciplinary research has become a matter of paramount importance for novel applications of nanomaterials in biology and medicine. As such, many disciplines-physics, chemistry, microbiology, cell biology, and material science-all contribute to the design, synthesis and fabrication of functional and biocompatible devices at the nanometer scale. Since the most areas of cell biology and biomedicine deal with functional entities such as DNA and proteins, mimicry of these structures and function in the nanosize range offers exciting opportunities for the development of biosensors, biochips, and bioplatforms. In this report we highlight the potential benefits and challenges that arise in the manufacture of biocompatible nanoparticles and nano-networks that can be coupled with biological objects. Among the challenges facing us are those concerned with making the necessary advances in enabling affordability, innovation, and quality of manufactured nanodevices for rapid progress in the emerging field of bio-nanotechnology. The convergence of nanotechnology and biomedicine makes nanoscale research highly promising for new discoveries that can cost-effectively accelerate progress in moving from basic research to practical prototypes and products.

Transmission electron microscopy in molecular structural biology: A historical survey.

PubMed

Harris, J Robin

2015-09-01

In this personal, historic account of macromolecular transmission electron microscopy (TEM), published data from the 1940s through to recent times is surveyed, within the context of the remarkable progress that has been achieved during this time period. The evolution of present day molecular structural biology is described in relation to the associated biological disciplines. The contribution of numerous electron microscope pioneers to the development of the subject is discussed. The principal techniques for TEM specimen preparation, thin sectioning, metal shadowing, negative staining and plunge-freezing (vitrification) of thin aqueous samples are described, with a selection of published images to emphasise the virtues of each method. The development of digital image analysis and 3D reconstruction is described in detail as applied to electron crystallography and reconstructions from helical structures, 2D membrane crystals as well as single particle 3D reconstruction of icosahedral viruses and macromolecules. The on-going development of new software, algorithms and approaches is highlighted before specific examples of the historical progress of the structural biology of proteins and viruses are presented. Copyright © 2014 Elsevier Inc. All rights reserved.

Tech Prep II: Implementation Final Report.

ERIC Educational Resources Information Center

Brown, Jane A.

This document contains the final progress report on a tech prep implementation project and the Work Force Challenge 2000 Report developed during the project. The final report lists these major accomplishments: approximately 1,500 educators in grades K-12 were provided information concerning future global issues in the work force and the effects in…

40 CFR 60.1585 - What are my requirements for meeting increments of progress and achieving final compliance?

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY... or Before August 30, 1999 Model Rule-Increments of Progress § 60.1585 What are my requirements for...