Modeling biological disturbances in LANDIS: a module description and demonstration using spruce budworm

Treesearch

Brian R. Sturtevant; Eric J. Gustafson; Wei Li; Hong S. He

2004-01-01

Insects and diseases are common disturbance agents in forested ecosystems. Severe outbreaks can cause significant changes in tree species composition, age structure, and fuel conditions over broad areas. To investigate the role of biological disturbances in shaping forest landscapes over time, we constructed a new "biological disturbance agent" (BDA) module...

CADDIS Volume 4. Data Analysis: Predicting Environmental Conditions from Biological Observations (PECBO Appendix)

EPA Pesticide Factsheets

Overview of PECBO Module, using scripts to infer environmental conditions from biological observations, statistically estimating species-environment relationships, methods for inferring environmental conditions, statistical scripts in module.

Supporting High School Student Accomplishment of Biology Content Using Interactive Computer-Based Curricular Case Studies

NASA Astrophysics Data System (ADS)

Oliver, Joseph Steve; Hodges, Georgia W.; Moore, James N.; Cohen, Allan; Jang, Yoonsun; Brown, Scott A.; Kwon, Kyung A.; Jeong, Sophia; Raven, Sara P.; Jurkiewicz, Melissa; Robertson, Tom P.

2017-11-01

Research into the efficacy of modules featuring dynamic visualizations, case studies, and interactive learning environments is reported here. This quasi-experimental 2-year study examined the implementation of three interactive computer-based instructional modules within a curricular unit covering cellular biology concepts in an introductory high school biology course. The modules featured dynamic visualizations and focused on three processes that underlie much of cellular biology: diffusion, osmosis, and filtration. Pre-tests and post-tests were used to assess knowledge growth across the unit. A mixture Rasch model analysis of the post-test data revealed two groups of students. In both years of the study, a large proportion of the students were classified as low-achieving based on their pre-test scores. The use of the modules in the Cell Unit in year 2 was associated with a much larger proportion of the students having transitioned to the high-achieving group than in year 1. In year 2, the same teachers taught the same concepts as year 1 but incorporated the interactive computer-based modules into the cell biology unit of the curriculum. In year 2, 67% of students initially classified as low-achieving were classified as high-achieving at the end of the unit. Examination of responses to assessments embedded within the modules as well as post-test items linked transition to the high-achieving group with correct responses to items that both referenced the visualization and the contextualization of that visualization within the module. This study points to the importance of dynamic visualization within contextualized case studies as a means to support student knowledge acquisition in biology.

Retroactivity in the Context of Modularly Structured Biomolecular Systems

PubMed Central

Pantoja-Hernández, Libertad; Martínez-García, Juan Carlos

2015-01-01

Synthetic biology has intensively promoted the technical implementation of modular strategies in the fabrication of biological devices. Modules are considered as networks of reactions. The behavior displayed by biomolecular systems results from the information processes carried out by the interconnection of the involved modules. However, in natural systems, module wiring is not a free-of-charge process; as a consequence of interconnection, a reactive phenomenon called retroactivity emerges. This phenomenon is characterized by signals that propagate from downstream modules (the modules that receive the incoming signals upon interconnection) to upstream ones (the modules that send the signals upon interconnection). Such retroactivity signals, depending of their strength, may change and sometimes even disrupt the behavior of modular biomolecular systems. Thus, analysis of retroactivity effects in natural biological and biosynthetic systems is crucial to achieve a deeper understanding of how this interconnection between functionally characterized modules takes place and how it impacts the overall behavior of the involved cell. By discussing the modules interconnection in natural and synthetic biomolecular systems, we propose that such systems should be considered as quasi-modular. PMID:26137457

Efficacy of a Meiosis Learning Module Developed for the Virtual Cell Animation Collection.

PubMed

Goff, Eric E; Reindl, Katie M; Johnson, Christina; McClean, Phillip; Offerdahl, Erika G; Schroeder, Noah L; White, Alan R

2017-01-01

Recent reports calling for change in undergraduate biology education have resulted in the redesign of many introductory biology courses. Reports on one common change to course structure, the active-learning environment, have placed an emphasis on student preparation, noting that the positive outcomes of active learning in the classroom depend greatly on how well the student prepares before class. As a possible preparatory resource, we test the efficacy of a learning module developed for the Virtual Cell Animation Collection. This module presents the concepts of meiosis in an interactive, dynamic environment that has previously been shown to facilitate learning in introductory biology students. Participants ( n = 534) were enrolled in an introductory biology course and were presented the concepts of meiosis in one of two treatments: the interactive-learning module or a traditional lecture session. Analysis of student achievement shows that students who viewed the learning module as their only means of conceptual presentation scored significantly higher ( d = 0.40, p < 0.001) than students who only attended a traditional lecture on the topic. Our results show the animation-based learning module effectively conveyed meiosis conceptual understanding, which suggests that it may facilitate student learning outside the classroom. Moreover, these results have implications for instructors seeking to expand their arsenal of tools for "flipping" undergraduate biology courses. © 2017 E. E. Goff et al. CBE—Life Sciences Education © 2017 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).

Use of shuttle for life sciences

NASA Technical Reports Server (NTRS)

Mcgaughy, R. E.

1972-01-01

The use of the space shuttle in carrying out biological and medical research programs, with emphasis on the sortie module, is examined. Detailed descriptions are given of the goals of space life science disciplines, how the sortie can meet these goals, and what shuttle design features are necessary for a viable biological and medical experiment program. Conclusions show that the space shuttle sortie module is capable of accommodating all biological experiments contemplated at this time except for those involving large specimens or large populations of small animals; however, these experiments can be done with a specially designed module. It was also found that at least two weeks is required to do a meaningful survey of biological effects.

Efficacy of a Meiosis Learning Module Developed for the Virtual Cell Animation Collection

PubMed Central

Goff, Eric E.; Reindl, Katie M.; Johnson, Christina; McClean, Phillip; Offerdahl, Erika G.; Schroeder, Noah L.; White, Alan R.

2017-01-01

Recent reports calling for change in undergraduate biology education have resulted in the redesign of many introductory biology courses. Reports on one common change to course structure, the active-learning environment, have placed an emphasis on student preparation, noting that the positive outcomes of active learning in the classroom depend greatly on how well the student prepares before class. As a possible preparatory resource, we test the efficacy of a learning module developed for the Virtual Cell Animation Collection. This module presents the concepts of meiosis in an interactive, dynamic environment that has previously been shown to facilitate learning in introductory biology students. Participants (n = 534) were enrolled in an introductory biology course and were presented the concepts of meiosis in one of two treatments: the interactive-learning module or a traditional lecture session. Analysis of student achievement shows that students who viewed the learning module as their only means of conceptual presentation scored significantly higher (d = 0.40, p < 0.001) than students who only attended a traditional lecture on the topic. Our results show the animation-based learning module effectively conveyed meiosis conceptual understanding, which suggests that it may facilitate student learning outside the classroom. Moreover, these results have implications for instructors seeking to expand their arsenal of tools for “flipping” undergraduate biology courses. PMID:28188282

Biomedical Potential of mTOR Modulation by Nanoparticles.

PubMed

Hulea, Laura; Markovic, Zoran; Topisirovic, Ivan; Simmet, Thomas; Trajkovic, Vladimir

2016-05-01

Modulation of the mammalian target of rapamycin (mTOR), the principal regulator of cellular homeostasis, underlies the biological effects of engineered nanoparticles, including regulation of cell death/survival and metabolic responses. Understanding the mechanisms and biological actions of nanoparticle-mediated mTOR modulation may help in developing safe and efficient nanotherapeutics to fight human disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Effectiveness of a Virtual Field Trip (VFT) Module in Learning Biology

ERIC Educational Resources Information Center

Haris, Norbaizura; Osman, Kamisah

2015-01-01

Virtual Field Trip is a computer aided module of science developed to study the Colonisation and Succession in Mangrove Swamps, as an alternative to the real field trip in Form for Biology. This study is to identify the effectiveness of the Virtual Field Trip (VFT) module towards the level of achievement in the formative test for this topic. This…

Hybrid coexpression link similarity graph clustering for mining biological modules from multiple gene expression datasets.

PubMed

Salem, Saeed; Ozcaglar, Cagri

2014-01-01

Advances in genomic technologies have enabled the accumulation of vast amount of genomic data, including gene expression data for multiple species under various biological and environmental conditions. Integration of these gene expression datasets is a promising strategy to alleviate the challenges of protein functional annotation and biological module discovery based on a single gene expression data, which suffers from spurious coexpression. We propose a joint mining algorithm that constructs a weighted hybrid similarity graph whose nodes are the coexpression links. The weight of an edge between two coexpression links in this hybrid graph is a linear combination of the topological similarities and co-appearance similarities of the corresponding two coexpression links. Clustering the weighted hybrid similarity graph yields recurrent coexpression link clusters (modules). Experimental results on Human gene expression datasets show that the reported modules are functionally homogeneous as evident by their enrichment with biological process GO terms and KEGG pathways.

Genomic Heterogeneity of Osteosarcoma - Shift from Single Candidates to Functional Modules

PubMed Central

Maugg, Doris; Eckstein, Gertrud; Baumhoer, Daniel; Nathrath, Michaela; Korsching, Eberhard

2015-01-01

Osteosarcoma (OS), a bone tumor, exhibit a complex karyotype. On the genomic level a highly variable degree of alterations in nearly all chromosomal regions and between individual tumors is observable. This hampers the identification of common drivers in OS biology. To identify the common molecular mechanisms involved in the maintenance of OS, we follow the hypothesis that all the copy number-associated differences between the patients are intercepted on the level of the functional modules. The implementation is based on a network approach utilizing copy number associated genes in OS, paired expression data and protein interaction data. The resulting functional modules of tightly connected genes were interpreted regarding their biological functions in OS and their potential prognostic significance. We identified an osteosarcoma network assembling well-known and lesser-known candidates. The derived network shows a significant connectivity and modularity suggesting that the genes affected by the heterogeneous genetic alterations share the same biological context. The network modules participate in several critical aspects of cancer biology like DNA damage response, cell growth, and cell motility which is in line with the hypothesis of specifically deregulated but functional modules in cancer. Further, we could deduce genes with possible prognostic significance in OS for further investigation (e.g. EZR, CDKN2A, MAP3K5). Several of those module genes were located on chromosome 6q. The given systems biological approach provides evidence that heterogeneity on the genomic and expression level is ordered by the biological system on the level of the functional modules. Different genomic aberrations are pointing to the same cellular network vicinity to form vital, but already neoplastically altered, functional modules maintaining OS. This observation, exemplarily now shown for OS, has been under discussion already for a longer time, but often in a hypothetical manner, and can here be exemplified for OS. PMID:25848766

Synthetic biology: new engineering rules for an emerging discipline

PubMed Central

Andrianantoandro, Ernesto; Basu, Subhayu; Karig, David K; Weiss, Ron

2006-01-01

Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development. PMID:16738572

Synthetic biology: new engineering rules for an emerging discipline.

PubMed

Andrianantoandro, Ernesto; Basu, Subhayu; Karig, David K; Weiss, Ron

2006-01-01

Synthetic biologists engineer complex artificial biological systems to investigate natural biological phenomena and for a variety of applications. We outline the basic features of synthetic biology as a new engineering discipline, covering examples from the latest literature and reflecting on the features that make it unique among all other existing engineering fields. We discuss methods for designing and constructing engineered cells with novel functions in a framework of an abstract hierarchy of biological devices, modules, cells, and multicellular systems. The classical engineering strategies of standardization, decoupling, and abstraction will have to be extended to take into account the inherent characteristics of biological devices and modules. To achieve predictability and reliability, strategies for engineering biology must include the notion of cellular context in the functional definition of devices and modules, use rational redesign and directed evolution for system optimization, and focus on accomplishing tasks using cell populations rather than individual cells. The discussion brings to light issues at the heart of designing complex living systems and provides a trajectory for future development.

Object-based attentional modulation of biological motion processing: spatiotemporal dynamics using functional magnetic resonance imaging and electroencephalography.

PubMed

Safford, Ashley S; Hussey, Elizabeth A; Parasuraman, Raja; Thompson, James C

2010-07-07

Although it is well documented that the ability to perceive biological motion is mediated by the lateral temporal cortex, whether and when neural activity in this brain region is modulated by attention is unknown. In particular, it is unclear whether the processing of biological motion requires attention or whether such stimuli are processed preattentively. Here, we used functional magnetic resonance imaging, high-density electroencephalography, and cortically constrained source estimation methods to investigate the spatiotemporal effects of attention on the processing of biological motion. Directing attention to tool motion in overlapping movies of biological motion and tool motion suppressed the blood oxygenation level-dependent (BOLD) response of the right superior temporal sulcus (STS)/middle temporal gyrus (MTG), while directing attention to biological motion suppressed the BOLD response of the left inferior temporal sulcus (ITS)/MTG. Similarly, category-based modulation of the cortical current source density estimates from the right STS/MTG and left ITS was observed beginning at approximately 450 ms following stimulus onset. Our results indicate that the cortical processing of biological motion is strongly modulated by attention. These findings argue against preattentive processing of biological motion in the presence of stimuli that compete for attention. Our findings also suggest that the attention-based segregation of motion category-specific responses only emerges relatively late (several hundred milliseconds) in processing.

How MAP kinase modules function as robust, yet adaptable, circuits.

PubMed

Tian, Tianhai; Harding, Angus

2014-01-01

Genetic and biochemical studies have revealed that the diversity of cell types and developmental patterns evident within the animal kingdom is generated by a handful of conserved, core modules. Core biological modules must be robust, able to maintain functionality despite perturbations, and yet sufficiently adaptable for random mutations to generate phenotypic variation during evolution. Understanding how robust, adaptable modules have influenced the evolution of eukaryotes will inform both evolutionary and synthetic biology. One such system is the MAP kinase module, which consists of a 3-tiered kinase circuit configuration that has been evolutionarily conserved from yeast to man. MAP kinase signal transduction pathways are used across eukaryotic phyla to drive biological functions that are crucial for life. Here we ask the fundamental question, why do MAPK modules follow a conserved 3-tiered topology rather than some other number? Using computational simulations, we identify a fundamental 2-tiered circuit topology that can be readily reconfigured by feedback loops and scaffolds to generate diverse signal outputs. When this 2-kinase circuit is connected to proximal input kinases, a 3-tiered modular configuration is created that is both robust and adaptable, providing a biological circuit that can regulate multiple phenotypes and maintain functionality in an uncertain world. We propose that the 3-tiered signal transduction module has been conserved through positive selection, because it facilitated the generation of phenotypic variation during eukaryotic evolution.

How MAP kinase modules function as robust, yet adaptable, circuits

PubMed Central

Tian, Tianhai; Harding, Angus

2014-01-01

Genetic and biochemical studies have revealed that the diversity of cell types and developmental patterns evident within the animal kingdom is generated by a handful of conserved, core modules. Core biological modules must be robust, able to maintain functionality despite perturbations, and yet sufficiently adaptable for random mutations to generate phenotypic variation during evolution. Understanding how robust, adaptable modules have influenced the evolution of eukaryotes will inform both evolutionary and synthetic biology. One such system is the MAP kinase module, which consists of a 3-tiered kinase circuit configuration that has been evolutionarily conserved from yeast to man. MAP kinase signal transduction pathways are used across eukaryotic phyla to drive biological functions that are crucial for life. Here we ask the fundamental question, why do MAPK modules follow a conserved 3-tiered topology rather than some other number? Using computational simulations, we identify a fundamental 2-tiered circuit topology that can be readily reconfigured by feedback loops and scaffolds to generate diverse signal outputs. When this 2-kinase circuit is connected to proximal input kinases, a 3-tiered modular configuration is created that is both robust and adaptable, providing a biological circuit that can regulate multiple phenotypes and maintain functionality in an uncertain world. We propose that the 3-tiered signal transduction module has been conserved through positive selection, because it facilitated the generation of phenotypic variation during eukaryotic evolution. PMID:25483189

Evidence of Rentian Scaling of Functional Modules in Diverse Biological Networks.

PubMed

How, Javier J; Navlakha, Saket

2018-06-12

Biological networks have long been known to be modular, containing sets of nodes that are highly connected internally. Less emphasis, however, has been placed on understanding how intermodule connections are distributed within a network. Here, we borrow ideas from engineered circuit design and study Rentian scaling, which states that the number of external connections between nodes in different modules is related to the number of nodes inside the modules by a power-law relationship. We tested this property in a broad class of molecular networks, including protein interaction networks for six species and gene regulatory networks for 41 human and 25 mouse cell types. Using evolutionarily defined modules corresponding to known biological processes in the cell, we found that all networks displayed Rentian scaling with a broad range of exponents. We also found evidence for Rentian scaling in functional modules in the Caenorhabditis elegans neural network, but, interestingly, not in three different social networks, suggesting that this property does not inevitably emerge. To understand how such scaling may have arisen evolutionarily, we derived a new graph model that can generate Rentian networks given a target Rent exponent and a module decomposition as inputs. Overall, our work uncovers a new principle shared by engineered circuits and biological networks.

A new multi-scale method to reveal hierarchical modular structures in biological networks.

PubMed

Jiao, Qing-Ju; Huang, Yan; Shen, Hong-Bin

2016-11-15

Biological networks are effective tools for studying molecular interactions. Modular structure, in which genes or proteins may tend to be associated with functional modules or protein complexes, is a remarkable feature of biological networks. Mining modular structure from biological networks enables us to focus on a set of potentially important nodes, which provides a reliable guide to future biological experiments. The first fundamental challenge in mining modular structure from biological networks is that the quality of the observed network data is usually low owing to noise and incompleteness in the obtained networks. The second problem that poses a challenge to existing approaches to the mining of modular structure is that the organization of both functional modules and protein complexes in networks is far more complicated than was ever thought. For instance, the sizes of different modules vary considerably from each other and they often form multi-scale hierarchical structures. To solve these problems, we propose a new multi-scale protocol for mining modular structure (named ISIMB) driven by a node similarity metric, which works in an iteratively converged space to reduce the effects of the low data quality of the observed network data. The multi-scale node similarity metric couples both the local and the global topology of the network with a resolution regulator. By varying this resolution regulator to give different weightings to the local and global terms in the metric, the ISIMB method is able to fit the shape of modules and to detect them on different scales. Experiments on protein-protein interaction and genetic interaction networks show that our method can not only mine functional modules and protein complexes successfully, but can also predict functional modules from specific to general and reveal the hierarchical organization of protein complexes.

Comparison of Modules of Wild Type and Mutant Huntingtin and TP53 Protein Interaction Networks: Implications in Biological Processes and Functions

PubMed Central

Basu, Mahashweta; Bhattacharyya, Nitai P.; Mohanty, Pradeep K.

2013-01-01

Disease-causing mutations usually change the interacting partners of mutant proteins. In this article, we propose that the biological consequences of mutation are directly related to the alteration of corresponding protein protein interaction networks (PPIN). Mutation of Huntingtin (HTT) which causes Huntington's disease (HD) and mutations to TP53 which is associated with different cancers are studied as two example cases. We construct the PPIN of wild type and mutant proteins separately and identify the structural modules of each of the networks. The functional role of these modules are then assessed by Gene Ontology (GO) enrichment analysis for biological processes (BPs). We find that a large number of significantly enriched () GO terms in mutant PPIN were absent in the wild type PPIN indicating the gain of BPs due to mutation. Similarly some of the GO terms enriched in wild type PPIN cease to exist in the modules of mutant PPIN, representing the loss. GO terms common in modules of mutant and wild type networks indicate both loss and gain of BPs. We further assign relevant biological function(s) to each module by classifying the enriched GO terms associated with it. It turns out that most of these biological functions in HTT networks are already known to be altered in HD and those of TP53 networks are altered in cancers. We argue that gain of BPs, and the corresponding biological functions, are due to new interacting partners acquired by mutant proteins. The methodology we adopt here could be applied to genetic diseases where mutations alter the ability of the protein to interact with other proteins. PMID:23741403

Bi-Fi: an embedded sensor/system architecture for REMOTE biological monitoring.

PubMed

Farshchi, Shahin; Pesterev, Aleksey; Nuyujukian, Paul H; Mody, Istvan; Judy, Jack W

2007-11-01

Wireless-enabled processor modules intended for communicating low-frequency phenomena (i.e., temperature, humidity, and ambient light) have been enabled to acquire and transmit multiple biological signals in real time, which has been achieved by using computationally efficient data acquisition, filtering, and compression algorithms, and interfacing the modules with biological interface hardware. The sensor modules can acquire and transmit raw biological signals at a rate of 32 kb/s, which is near the hardware limit of the modules. Furthermore, onboard signal processing enables one channel, sampled at a rate of 4000 samples/s at 12-bit resolution, to be compressed via adaptive differential-pulse-code modulation (ADPCM) and transmitted in real time. In addition, the sensors can be configured to filter and transmit individual time-referenced "spike" waveforms, or to transmit the spike height and width for alleviating network traffic and increasing battery life. The system is capable of acquiring eight channels of analog signals as well as data via an asynchronous serial connection. A back-end server archives the biological data received via networked gateway sensors, and hosts them to a client application that enables users to browse recorded data. The system also acquires, filters, and transmits oxygen saturation and pulse rate via a commercial-off-the-shelf interface board. The system architecture can be configured for performing real-time nonobtrusive biological monitoring of humans or rodents. This paper demonstrates that low-power, computational, and bandwidth-constrained wireless-enabled platforms can indeed be leveraged for wireless biosignal monitoring.

Applications of systems approaches in the study of rheumatic diseases.

PubMed

Kim, Ki-Jo; Lee, Saseong; Kim, Wan-Uk

2015-03-01

The complex interaction of molecules within a biological system constitutes a functional module. These modules are then acted upon by both internal and external factors, such as genetic and environmental stresses, which under certain conditions can manifest as complex disease phenotypes. Recent advances in high-throughput biological analyses, in combination with improved computational methods for data enrichment, functional annotation, and network visualization, have enabled a much deeper understanding of the mechanisms underlying important biological processes by identifying functional modules that are temporally and spatially perturbed in the context of disease development. Systems biology approaches such as these have produced compelling observations that would be impossible to replicate using classical methodologies, with greater insights expected as both the technology and methods improve in the coming years. Here, we examine the use of systems biology and network analysis in the study of a wide range of rheumatic diseases to better understand the underlying molecular and clinical features.

Dense module enumeration in biological networks

NASA Astrophysics Data System (ADS)

Tsuda, Koji; Georgii, Elisabeth

2009-12-01

Analysis of large networks is a central topic in various research fields including biology, sociology, and web mining. Detection of dense modules (a.k.a. clusters) is an important step to analyze the networks. Though numerous methods have been proposed to this aim, they often lack mathematical rigorousness. Namely, there is no guarantee that all dense modules are detected. Here, we present a novel reverse-search-based method for enumerating all dense modules. Furthermore, constraints from additional data sources such as gene expression profiles or customer profiles can be integrated, so that we can systematically detect dense modules with interesting profiles. We report successful applications in human protein interaction network analyses.

CUFID-query: accurate network querying through random walk based network flow estimation.

PubMed

Jeong, Hyundoo; Qian, Xiaoning; Yoon, Byung-Jun

2017-12-28

Functional modules in biological networks consist of numerous biomolecules and their complicated interactions. Recent studies have shown that biomolecules in a functional module tend to have similar interaction patterns and that such modules are often conserved across biological networks of different species. As a result, such conserved functional modules can be identified through comparative analysis of biological networks. In this work, we propose a novel network querying algorithm based on the CUFID (Comparative network analysis Using the steady-state network Flow to IDentify orthologous proteins) framework combined with an efficient seed-and-extension approach. The proposed algorithm, CUFID-query, can accurately detect conserved functional modules as small subnetworks in the target network that are expected to perform similar functions to the given query functional module. The CUFID framework was recently developed for probabilistic pairwise global comparison of biological networks, and it has been applied to pairwise global network alignment, where the framework was shown to yield accurate network alignment results. In the proposed CUFID-query algorithm, we adopt the CUFID framework and extend it for local network alignment, specifically to solve network querying problems. First, in the seed selection phase, the proposed method utilizes the CUFID framework to compare the query and the target networks and to predict the probabilistic node-to-node correspondence between the networks. Next, the algorithm selects and greedily extends the seed in the target network by iteratively adding nodes that have frequent interactions with other nodes in the seed network, in a way that the conductance of the extended network is maximally reduced. Finally, CUFID-query removes irrelevant nodes from the querying results based on the personalized PageRank vector for the induced network that includes the fully extended network and its neighboring nodes. Through extensive performance evaluation based on biological networks with known functional modules, we show that CUFID-query outperforms the existing state-of-the-art algorithms in terms of prediction accuracy and biological significance of the predictions.

Hybrid coexpression link similarity graph clustering for mining biological modules from multiple gene expression datasets

PubMed Central

2014-01-01

Background Advances in genomic technologies have enabled the accumulation of vast amount of genomic data, including gene expression data for multiple species under various biological and environmental conditions. Integration of these gene expression datasets is a promising strategy to alleviate the challenges of protein functional annotation and biological module discovery based on a single gene expression data, which suffers from spurious coexpression. Results We propose a joint mining algorithm that constructs a weighted hybrid similarity graph whose nodes are the coexpression links. The weight of an edge between two coexpression links in this hybrid graph is a linear combination of the topological similarities and co-appearance similarities of the corresponding two coexpression links. Clustering the weighted hybrid similarity graph yields recurrent coexpression link clusters (modules). Experimental results on Human gene expression datasets show that the reported modules are functionally homogeneous as evident by their enrichment with biological process GO terms and KEGG pathways. PMID:25221624

Frontotemporal dementia: insights into the biological underpinnings of disease through gene co-expression network analysis.

PubMed

Ferrari, Raffaele; Forabosco, Paola; Vandrovcova, Jana; Botía, Juan A; Guelfi, Sebastian; Warren, Jason D; Momeni, Parastoo; Weale, Michael E; Ryten, Mina; Hardy, John

2016-02-24

In frontotemporal dementia (FTD) there is a critical lack in the understanding of biological and molecular mechanisms involved in disease pathogenesis. The heterogeneous genetic features associated with FTD suggest that multiple disease-mechanisms are likely to contribute to the development of this neurodegenerative condition. We here present a systems biology approach with the scope of i) shedding light on the biological processes potentially implicated in the pathogenesis of FTD and ii) identifying novel potential risk factors for FTD. We performed a gene co-expression network analysis of microarray expression data from 101 individuals without neurodegenerative diseases to explore regional-specific co-expression patterns in the frontal and temporal cortices for 12 genes (MAPT, GRN, CHMP2B, CTSC, HLA-DRA, TMEM106B, C9orf72, VCP, UBQLN2, OPTN, TARDBP and FUS) associated with FTD and we then carried out gene set enrichment and pathway analyses, and investigated known protein-protein interactors (PPIs) of FTD-genes products. Gene co-expression networks revealed that several FTD-genes (such as MAPT and GRN, CTSC and HLA-DRA, TMEM106B, and C9orf72, VCP, UBQLN2 and OPTN) were clustering in modules of relevance in the frontal and temporal cortices. Functional annotation and pathway analyses of such modules indicated enrichment for: i) DNA metabolism, i.e. transcription regulation, DNA protection and chromatin remodelling (MAPT and GRN modules); ii) immune and lysosomal processes (CTSC and HLA-DRA modules), and; iii) protein meta/catabolism (C9orf72, VCP, UBQLN2 and OPTN, and TMEM106B modules). PPI analysis supported the results of the functional annotation and pathway analyses. This work further characterizes known FTD-genes and elaborates on their biological relevance to disease: not only do we indicate likely impacted regional-specific biological processes driven by FTD-genes containing modules, but also do we suggest novel potential risk factors among the FTD-genes interactors as targets for further mechanistic characterization in hypothesis driven cell biology work.

Cancer Cell Biology: A Student-Centered Instructional Module Exploring the Use of Multimedia to Enrich Interactive, Constructivist Learning of Science

PubMed Central

Bockholt, Susanne M.; West, J. Paige; Bollenbacher, Walter E.

2003-01-01

Multimedia has the potential of providing bioscience education novel learning environments and pedagogy applications to foster student interest, involve students in the research process, advance critical thinking/problem-solving skills, and develop conceptual understanding of biological topics. Cancer Cell Biology, an interactive, multimedia, problem-based module, focuses on how mutations in protooncogenes and tumor suppressor genes can lead to uncontrolled cell proliferation by engaging students as research scientists/physicians with the task of diagnosing the molecular basis of tumor growth for a group of patients. The process of constructing the module, which was guided by scientist and student feedback/responses, is described. The completed module and insights gained from its development are presented as a potential “multimedia pedagogy” for the development of other multimedia science learning environments. PMID:12822037

A Systems Approach to Biology (SAB).

ERIC Educational Resources Information Center

Bush, Kenneth H.; And Others

This pupil's study guide is intended to be used with audio-taped biology modules. Each of the units (on laboratory techniques, plant and animal diversity, chemistry, cells, energy, microbiology, genetics, and development) contains an abstract providing an overview of the unit, the rationale and performance objectives for each module, questions to…

Hadfield prepares to insert biological samples in the MELFI-1

NASA Image and Video Library

2013-01-07

View of Canadian Space Agency (CSA) Chris Hadfield,Expedition 34 Flight Engineer (FE),preparing to insert biological samples in the Minus Eighty Laboratory Freezer for International Space Station (ISS) - (MELFI-1),in the Japanese Experiment Module (JEM) Pressurized Module (JPM). Photo was taken during Expedition 34.

Development and Assessment of Modules to Integrate Quantitative Skills in Introductory Biology Courses

ERIC Educational Resources Information Center

Hoffman, Kathleen; Leupen, Sarah; Dowell, Kathy; Kephart, Kerrie; Leips, Jeff

2016-01-01

Redesigning undergraduate biology courses to integrate quantitative reasoning and skill development is critical to prepare students for careers in modern medicine and scientific research. In this paper, we report on the development, implementation, and assessment of stand-alone modules that integrate quantitative reasoning into introductory…

A Streamlined Molecular Biology Module for Undergraduate Biochemistry Labs

ERIC Educational Resources Information Center

Muth, Gregory W.; Chihade, Joseph W.

2008-01-01

Site-directed mutagenesis and other molecular biology techniques, including plasmid manipulation and restriction analysis, are commonly used tools in the biochemistry research laboratory. In redesigning our biochemistry lab curricula, we sought to integrate these techniques into a term-long, project-based course. In the module presented here,…

First biological evaluation of developed 3-benzyloxyfluorenes as novel class of MDR modulators.

PubMed

Krug, Martin; Voigt, Burkhardt; Baumert, Christiane; Lüpken, Ralf; Molnár, Joséf; Hilgeroth, Andreas

2010-06-01

A series of 3-benzyloxy-1-aza-9-oxafluorenes has been synthesized and biologically evaluated as novel MDR modulators. The concentration dependent inhibition of the efflux pump ABCB1 (P-glycoprotein) has been characterized and is discussed in relation to calculated lipophilicity data. Instead of the molecular lipophilicity the exact positioning of functional groups was found decisive for the biological activities. Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.

Functional Module Analysis for Gene Coexpression Networks with Network Integration.

PubMed

Zhang, Shuqin; Zhao, Hongyu; Ng, Michael K

2015-01-01

Network has been a general tool for studying the complex interactions between different genes, proteins, and other small molecules. Module as a fundamental property of many biological networks has been widely studied and many computational methods have been proposed to identify the modules in an individual network. However, in many cases, a single network is insufficient for module analysis due to the noise in the data or the tuning of parameters when building the biological network. The availability of a large amount of biological networks makes network integration study possible. By integrating such networks, more informative modules for some specific disease can be derived from the networks constructed from different tissues, and consistent factors for different diseases can be inferred. In this paper, we have developed an effective method for module identification from multiple networks under different conditions. The problem is formulated as an optimization model, which combines the module identification in each individual network and alignment of the modules from different networks together. An approximation algorithm based on eigenvector computation is proposed. Our method outperforms the existing methods, especially when the underlying modules in multiple networks are different in simulation studies. We also applied our method to two groups of gene coexpression networks for humans, which include one for three different cancers, and one for three tissues from the morbidly obese patients. We identified 13 modules with three complete subgraphs, and 11 modules with two complete subgraphs, respectively. The modules were validated through Gene Ontology enrichment and KEGG pathway enrichment analysis. We also showed that the main functions of most modules for the corresponding disease have been addressed by other researchers, which may provide the theoretical basis for further studying the modules experimentally.

A biological approach to assembling tissue modules through endothelial capillary network formation.

PubMed

Riesberg, Jeremiah J; Shen, Wei

2015-09-01

To create functional tissues having complex structures, bottom-up approaches to assembling small tissue modules into larger constructs have been emerging. Most of these approaches are based on chemical reactions or physical interactions at the interface between tissue modules. Here we report a biological assembly approach to integrate small tissue modules through endothelial capillary network formation. When adjacent tissue modules contain appropriate extracellular matrix materials and cell types that support robust endothelial capillary network formation, capillary tubules form and grow across the interface, resulting in assembly of the modules into a single, larger construct. It was shown that capillary networks formed in modules of dense fibrin gels seeded with human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (MSCs); adjacent modules were firmly assembled into an integrated construct having a strain to failure of 117 ± 26%, a tensile strength of 2208 ± 83 Pa and a Young's modulus of 2548 ± 574 Pa. Under the same culture conditions, capillary networks were absent in modules of dense fibrin gels seeded with either HUVECs or MSCs alone; adjacent modules disconnected even when handled gently. This biological assembly approach eliminates the need for chemical reactions or physical interactions and their associated limitations. In addition, the integrated constructs are prevascularized, and therefore this bottom-up assembly approach may also help address the issue of vascularization, another key challenge in tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.

Teaching About "Brain and Learning" in High School Biology Classes: Effects on Teachers' Knowledge and Students' Theory of Intelligence.

PubMed

Dekker, Sanne; Jolles, Jelle

2015-01-01

This study evaluated a new teaching module about "Brain and Learning" using a controlled design. The module was implemented in high school biology classes and comprised three lessons: (1) brain processes underlying learning; (2) neuropsychological development during adolescence; and (3) lifestyle factors that influence learning performance. Participants were 32 biology teachers who were interested in "Brain and Learning" and 1241 students in grades 8-9. Teachers' knowledge and students' beliefs about learning potential were examined using online questionnaires. Results indicated that before intervention, biology teachers were significantly less familiar with how the brain functions and develops than with its structure and with basic neuroscientific concepts (46 vs. 75% correct answers). After intervention, teachers' knowledge of "Brain and Learning" had significantly increased (64%), and more students believed that intelligence is malleable (incremental theory). This emphasizes the potential value of a short teaching module, both for improving biology teachers' insights into "Brain and Learning," and for changing students' beliefs about intelligence.

Nanoparticle interface to biology: applications in probing and modulating biological processes.

PubMed

Kah, James Chen Yong; Yeo, Eugenia Li Ling; Koh, Wee Ling; Poinard, Barbara Elodie Ariane; Neo, Dawn Jing Hui

2013-01-01

Nanomaterials can be considered as "pseudo" subcellular entities that are similar to endogenous biomolecules because of their size and ability to interact with other biomolecules. The interaction between nanoparticles and biomolecules gives rise to the nano-bio interface between a nanoparticle and its biological environment. This is often defined in terms of the biomolecules that are present on the surface of the nanoparticles. The nano-bio interface alters the surface characteristics and is what the biological system sees and interacts with. The nanoparticle can thus be viewed as a "scaffold" to which molecules are attached. Intelligent design of this nano-bio interface is therefore crucial to the functionality of nanoscale systems in biology. In this review, we discuss the most common nano-bio interfaces formed from molecules including DNA, polymers, proteins, and antibodies, and discuss their applications in probing and modulating biological processes. We focus our discussion on the nano-bio interface formed on gold nanoparticles as our nanoparticle "scaffold" of interest in part because of our research interest as well as their unique physicochemical properties. While not exhaustive, this review provides a good overview of the latest advances in the use of gold nanomaterial interface to probe and modulate biological processes.

Toxins, Targets, and Triggers: An Overview of Toxin-Antitoxin Biology.

PubMed

Harms, Alexander; Brodersen, Ditlev Egeskov; Mitarai, Namiko; Gerdes, Kenn

2018-06-07

Bacterial toxin-antitoxin (TA) modules are abundant genetic elements that encode a toxin protein capable of inhibiting cell growth and an antitoxin that counteracts the toxin. The majority of toxins are enzymes that interfere with translation or DNA replication, but a wide variety of molecular activities and cellular targets have been described. Antitoxins are proteins or RNAs that often control their cognate toxins through direct interactions and, in conjunction with other signaling elements, through transcriptional and translational regulation of TA module expression. Three major biological functions of TA modules have been discovered, post-segregational killing ("plasmid addiction"), abortive infection (bacteriophage immunity through altruistic suicide), and persister formation (antibiotic tolerance through dormancy). In this review, we summarize the current state of the field and highlight how multiple levels of regulation shape the conditions of toxin activation to achieve the different biological functions of TA modules. Copyright © 2018 Elsevier Inc. All rights reserved.

CommWalker: correctly evaluating modules in molecular networks in light of annotation bias.

PubMed

Luecken, M D; Page, M J T; Crosby, A J; Mason, S; Reinert, G; Deane, C M

2018-03-15

Detecting novel functional modules in molecular networks is an important step in biological research. In the absence of gold standard functional modules, functional annotations are often used to verify whether detected modules/communities have biological meaning. However, as we show, the uneven distribution of functional annotations means that such evaluation methods favor communities of well-studied proteins. We propose a novel framework for the evaluation of communities as functional modules. Our proposed framework, CommWalker, takes communities as inputs and evaluates them in their local network environment by performing short random walks. We test CommWalker's ability to overcome annotation bias using input communities from four community detection methods on two protein interaction networks. We find that modules accepted by CommWalker are similarly co-expressed as those accepted by current methods. Crucially, CommWalker performs well not only in well-annotated regions, but also in regions otherwise obscured by poor annotation. CommWalker community prioritization both faithfully captures well-validated communities and identifies functional modules that may correspond to more novel biology. The CommWalker algorithm is freely available at opig.stats.ox.ac.uk/resources or as a docker image on the Docker Hub at hub.docker.com/r/lueckenmd/commwalker/. deane@stats.ox.ac.uk. Supplementary data are available at Bioinformatics online.

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

Development and Assessment of Modules to Integrate Quantitative Skills in Introductory Biology Courses

PubMed Central

Hoffman, Kathleen; Leupen, Sarah; Dowell, Kathy; Kephart, Kerrie; Leips, Jeff

2016-01-01

Redesigning undergraduate biology courses to integrate quantitative reasoning and skill development is critical to prepare students for careers in modern medicine and scientific research. In this paper, we report on the development, implementation, and assessment of stand-alone modules that integrate quantitative reasoning into introductory biology courses. Modules are designed to improve skills in quantitative numeracy, interpreting data sets using visual tools, and making inferences about biological phenomena using mathematical/statistical models. We also examine demographic/background data that predict student improvement in these skills through exposure to these modules. We carried out pre/postassessment tests across four semesters and used student interviews in one semester to examine how students at different levels approached quantitative problems. We found that students improved in all skills in most semesters, although there was variation in the degree of improvement among skills from semester to semester. One demographic variable, transfer status, stood out as a major predictor of the degree to which students improved (transfer students achieved much lower gains every semester, despite the fact that pretest scores in each focus area were similar between transfer and nontransfer students). We propose that increased exposure to quantitative skill development in biology courses is effective at building competency in quantitative reasoning. PMID:27146161

AIM: A comprehensive Arabidopsis Interactome Module database and related interologs in plants

USDA-ARS?s Scientific Manuscript database

Systems biology analysis of protein modules is important for understanding the functional relationships between proteins in the interactome. Here, we present a comprehensive database named AIM for Arabidopsis (Arabidopsis thaliana) interactome modules. The database contains almost 250,000 modules th...

Differential Scanning Calorimetry Techniques: Applications in Biology and Nanoscience

PubMed Central

Gill, Pooria; Moghadam, Tahereh Tohidi; Ranjbar, Bijan

2010-01-01

This paper reviews the best-known differential scanning calorimetries (DSCs), such as conventional DSC, microelectromechanical systems-DSC, infrared-heated DSC, modulated-temperature DSC, gas flow-modulated DSC, parallel-nano DSC, pressure perturbation calorimetry, self-reference DSC, and high-performance DSC. Also, we describe here the most extensive applications of DSC in biology and nanoscience. PMID:21119929

Accommodating those Most at Risk. Responding to a Mismatch in Programme Selection Criteria and Foundation Biology Performance

NASA Astrophysics Data System (ADS)

Kirby, Nicola F.; Dempster, Edith R.

2015-12-01

In South Africa, foundation programmes are a well-established alternative access route to tertiary science study for educationally disadvantaged students. Student access to, and performance in, one such foundation programme has been researched by the authors seeking opportunities to improve student retention. The biology module in particular has been recognised to place students at risk of failing the foundation programme, thereby reducing throughput into mainstream science programmes. This study uses decision tree analysis to provide a detailed description of foundation biology student performance so that points of weakness and opportunities for remedial action may be pinpointed. While students' alternative-entry selection scores have previously been found to most effectively account for performance in the programme as a whole, no similar positive relationship was identified for any subgroup of students in the foundation biology module. Conversely, academic language proficiency in the medium of instruction (English), formerly found to play no role in overall student performance, was revealed as primary in explaining achievement in foundation biology, most adversely affecting students rendered particularly vulnerable by an additional academic and/or socio-economic disadvantage. A pass in the stand-alone foundation academic literacy module did not necessarily correspond to a pass in biology. Compromised by educational disadvantage, compounded by a mismatch in programme selection criteria and inadequate academic literacy support, discipline-specific, fundamental literacy development in the biology curriculum is proposed to enable students towards epistemic access in the module. Pending this intervention, formal access to mainstream study is unlikely for the foundation students most at risk of failure.

Prior knowledge guided active modules identification: an integrated multi-objective approach.

PubMed

Chen, Weiqi; Liu, Jing; He, Shan

2017-03-14

Active module, defined as an area in biological network that shows striking changes in molecular activity or phenotypic signatures, is important to reveal dynamic and process-specific information that is correlated with cellular or disease states. A prior information guided active module identification approach is proposed to detect modules that are both active and enriched by prior knowledge. We formulate the active module identification problem as a multi-objective optimisation problem, which consists two conflicting objective functions of maximising the coverage of known biological pathways and the activity of the active module simultaneously. Network is constructed from protein-protein interaction database. A beta-uniform-mixture model is used to estimate the distribution of p-values and generate scores for activity measurement from microarray data. A multi-objective evolutionary algorithm is used to search for Pareto optimal solutions. We also incorporate a novel constraints based on algebraic connectivity to ensure the connectedness of the identified active modules. Application of proposed algorithm on a small yeast molecular network shows that it can identify modules with high activities and with more cross-talk nodes between related functional groups. The Pareto solutions generated by the algorithm provides solutions with different trade-off between prior knowledge and novel information from data. The approach is then applied on microarray data from diclofenac-treated yeast cells to build network and identify modules to elucidate the molecular mechanisms of diclofenac toxicity and resistance. Gene ontology analysis is applied to the identified modules for biological interpretation. Integrating knowledge of functional groups into the identification of active module is an effective method and provides a flexible control of balance between pure data-driven method and prior information guidance.

Modifications of Glycans: Biological Significance and Therapeutic Opportunities

PubMed Central

Muthana, Saddam M.; Campbell, Christopher; Gildersleeve, Jeffrey C.

2012-01-01

Carbohydrates play a central role in a wide range of biological processes. As with nucleic acids and proteins, modifications of specific sites within the glycan chain can modulate a carbohydrate’s overall biological function. For example, acylation, methylation, sulfation, epimerization, and phosphorylation can occur at various positions within a carbohydrate to modulate bioactivity. Therefore, there is significant interest in identifying discrete carbohydrate modifications and understanding their biological effects. Additionally, enzymes that catalyze those modifications and proteins that bind modified glycans provide numerous targets for therapeutic intervention. This review will focus on modifications of glycans that occur after the oligomer/polymer has been assembled, generally referred to as postglycosylational modifications. PMID:22195988

Integrating pharmacology topics in high school biology and chemistry classes improves performance

NASA Astrophysics Data System (ADS)

Schwartz-Bloom, Rochelle D.; Halpin, Myra J.

2003-11-01

Although numerous programs have been developed for Grade Kindergarten through 12 science education, evaluation has been difficult owing to the inherent problems conducting controlled experiments in the typical classroom. Using a rigorous experimental design, we developed and tested a novel program containing a series of pharmacology modules (e.g., drug abuse) to help high school students learn basic principles in biology and chemistry. High school biology and chemistry teachers were recruited for the study and they attended a 1-week workshop to learn how to integrate pharmacology into their teaching. Working with university pharmacology faculty, they also developed classroom activities. The following year, teachers field-tested the pharmacology modules in their classrooms. Students in classrooms using the pharmacology topics scored significantly higher on a multiple choice test of basic biology and chemistry concepts compared with controls. Very large effect sizes (up to 1.27 standard deviations) were obtained when teachers used as many as four modules. In addition, biology students increased performance on chemistry questions and chemistry students increased performance on biology questions. Substantial gains in achievement may be made when high school students are taught science using topics that are interesting and relevant to their own lives.

Teaching About “Brain and Learning” in High School Biology Classes: Effects on Teachers' Knowledge and Students' Theory of Intelligence

PubMed Central

Dekker, Sanne; Jolles, Jelle

2015-01-01

This study evaluated a new teaching module about “Brain and Learning” using a controlled design. The module was implemented in high school biology classes and comprised three lessons: (1) brain processes underlying learning; (2) neuropsychological development during adolescence; and (3) lifestyle factors that influence learning performance. Participants were 32 biology teachers who were interested in “Brain and Learning” and 1241 students in grades 8–9. Teachers' knowledge and students' beliefs about learning potential were examined using online questionnaires. Results indicated that before intervention, biology teachers were significantly less familiar with how the brain functions and develops than with its structure and with basic neuroscientific concepts (46 vs. 75% correct answers). After intervention, teachers' knowledge of “Brain and Learning” had significantly increased (64%), and more students believed that intelligence is malleable (incremental theory). This emphasizes the potential value of a short teaching module, both for improving biology teachers' insights into “Brain and Learning,” and for changing students' beliefs about intelligence. PMID:26648900

Macro to microfluidics system for biological environmental monitoring.

PubMed

Delattre, Cyril; Allier, Cédric P; Fouillet, Yves; Jary, Dorothée; Bottausci, Frederic; Bouvier, Denis; Delapierre, Guillaume; Quinaud, Manuelle; Rival, Arnaud; Davoust, Laurent; Peponnet, Christine

2012-01-01

Biological environmental monitoring (BEM) is a growing field of research which challenges both microfluidics and system automation. The aim is to develop a transportable system with analysis throughput which satisfies the requirements: (i) fully autonomous, (ii) complete protocol integration from sample collection to final analysis, (iii) detection of diluted molecules or biological species in a large real life environmental sample volume, (iv) robustness and (v) flexibility and versatility. This paper discusses all these specifications in order to define an original fluidic architecture based on three connected modules, a sampling module, a sample preparation module and a detection module. The sample preparation module highly concentrates on the pathogens present in a few mL samples of complex and unknown solutions and purifies the pathogens' nucleic acids into a few μL of a controlled buffer. To do so, a two-step concentration protocol based on magnetic beads is automated in a reusable macro-to-micro fluidic system. The detection module is a PCR based miniaturized platform using digital microfluidics, where reactions are performed in 64 nL droplets handled by electrowetting on dielectric (EWOD) actuation. The design and manufacture of the two modules are reported as well as their respective performances. To demonstrate the integration of the complete protocol in the same system, first results of pathogen detection are shown. Copyright © 2012 Elsevier B.V. All rights reserved.

Identification of common coexpression modules based on quantitative network comparison.

PubMed

Jo, Yousang; Kim, Sanghyeon; Lee, Doheon

2018-06-13

Finding common molecular interactions from different samples is essential work to understanding diseases and other biological processes. Coexpression networks and their modules directly reflect sample-specific interactions among genes. Therefore, identification of common coexpression network or modules may reveal the molecular mechanism of complex disease or the relationship between biological processes. However, there has been no quantitative network comparison method for coexpression networks and we examined previous methods for other networks that cannot be applied to coexpression network. Therefore, we aimed to propose quantitative comparison methods for coexpression networks and to find common biological mechanisms between Huntington's disease and brain aging by the new method. We proposed two similarity measures for quantitative comparison of coexpression networks. Then, we performed experiments using known coexpression networks. We showed the validity of two measures and evaluated threshold values for similar coexpression network pairs from experiments. Using these similarity measures and thresholds, we quantitatively measured the similarity between disease-specific and aging-related coexpression modules and found similar Huntington's disease-aging coexpression module pairs. We identified similar Huntington's disease-aging coexpression module pairs and found that these modules are related to brain development, cell death, and immune response. It suggests that up-regulated cell signalling related cell death and immune/ inflammation response may be the common molecular mechanisms in the pathophysiology of HD and normal brain aging in the frontal cortex.

Linear motif-mediated interactions have contributed to the evolution of modularity in complex protein interaction networks.

PubMed

Kim, Inhae; Lee, Heetak; Han, Seong Kyu; Kim, Sanguk

2014-10-01

The modular architecture of protein-protein interaction (PPI) networks is evident in diverse species with a wide range of complexity. However, the molecular components that lead to the evolution of modularity in PPI networks have not been clearly identified. Here, we show that weak domain-linear motif interactions (DLIs) are more likely to connect different biological modules than strong domain-domain interactions (DDIs). This molecular division of labor is essential for the evolution of modularity in the complex PPI networks of diverse eukaryotic species. In particular, DLIs may compensate for the reduction in module boundaries that originate from increased connections between different modules in complex PPI networks. In addition, we show that the identification of biological modules can be greatly improved by including molecular characteristics of protein interactions. Our findings suggest that transient interactions have played a unique role in shaping the architecture and modularity of biological networks over the course of evolution.

AIM: a comprehensive Arabidopsis interactome module database and related interologs in plants.

PubMed

Wang, Yi; Thilmony, Roger; Zhao, Yunjun; Chen, Guoping; Gu, Yong Q

2014-01-01

Systems biology analysis of protein modules is important for understanding the functional relationships between proteins in the interactome. Here, we present a comprehensive database named AIM for Arabidopsis (Arabidopsis thaliana) interactome modules. The database contains almost 250,000 modules that were generated using multiple analysis methods and integration of microarray expression data. All the modules in AIM are well annotated using multiple gene function knowledge databases. AIM provides a user-friendly interface for different types of searches and offers a powerful graphical viewer for displaying module networks linked to the enrichment annotation terms. Both interactive Venn diagram and power graph viewer are integrated into the database for easy comparison of modules. In addition, predicted interologs from other plant species (homologous proteins from different species that share a conserved interaction module) are available for each Arabidopsis module. AIM is a powerful systems biology platform for obtaining valuable insights into the function of proteins in Arabidopsis and other plants using the modules of the Arabidopsis interactome. Database URL:http://probes.pw.usda.gov/AIM Published by Oxford University Press 2014. This work is written by US Government employees and is in the public domain in the US.

Development and Assessment of Modules to Integrate Quantitative Skills in Introductory Biology Courses.

PubMed

Hoffman, Kathleen; Leupen, Sarah; Dowell, Kathy; Kephart, Kerrie; Leips, Jeff

2016-01-01

Redesigning undergraduate biology courses to integrate quantitative reasoning and skill development is critical to prepare students for careers in modern medicine and scientific research. In this paper, we report on the development, implementation, and assessment of stand-alone modules that integrate quantitative reasoning into introductory biology courses. Modules are designed to improve skills in quantitative numeracy, interpreting data sets using visual tools, and making inferences about biological phenomena using mathematical/statistical models. We also examine demographic/background data that predict student improvement in these skills through exposure to these modules. We carried out pre/postassessment tests across four semesters and used student interviews in one semester to examine how students at different levels approached quantitative problems. We found that students improved in all skills in most semesters, although there was variation in the degree of improvement among skills from semester to semester. One demographic variable, transfer status, stood out as a major predictor of the degree to which students improved (transfer students achieved much lower gains every semester, despite the fact that pretest scores in each focus area were similar between transfer and nontransfer students). We propose that increased exposure to quantitative skill development in biology courses is effective at building competency in quantitative reasoning. © 2016 K. Hoffman, S. Leupen, et al. CBE—Life Sciences Education © 2016 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).

Recognizing Job Health Hazards. Module SH-08. Safety and Health.

ERIC Educational Resources Information Center

Center for Occupational Research and Development, Inc., Waco, TX.

This student module on recognizing job health hazards is one of 50 modules concerned with job safety and health. This module presents the four general categories of environmental conditions or stresses: chemical, physical, biological, and ergonomic. Following the introduction, 14 objectives (each keyed to a page in the text) the student is…

Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging.

PubMed

Afornali, Alessandro; Vecchi, Rodrigo de; Stuart, Rodrigo Makowiecky; Dieamant, Gustavo; Oliveira, Luciana Lima de; Brohem, Carla Abdo; Feferman, Israel Henrique Stokfisz; Fabrício, Lincoln Helder Zambaldi; Lorencini, Márcio

2013-01-01

The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly.

INfORM: Inference of NetwOrk Response Modules.

PubMed

Marwah, Veer Singh; Kinaret, Pia Anneli Sofia; Serra, Angela; Scala, Giovanni; Lauerma, Antti; Fortino, Vittorio; Greco, Dario

2018-06-15

Detecting and interpreting responsive modules from gene expression data by using network-based approaches is a common but laborious task. It often requires the application of several computational methods implemented in different software packages, forcing biologists to compile complex analytical pipelines. Here we introduce INfORM (Inference of NetwOrk Response Modules), an R shiny application that enables non-expert users to detect, evaluate and select gene modules with high statistical and biological significance. INfORM is a comprehensive tool for the identification of biologically meaningful response modules from consensus gene networks inferred by using multiple algorithms. It is accessible through an intuitive graphical user interface allowing for a level of abstraction from the computational steps. INfORM is freely available for academic use at https://github.com/Greco-Lab/INfORM. Supplementary data are available at Bioinformatics online.

Polymerase chain reaction system

DOEpatents

Benett, William J.; Richards, James B.; Stratton, Paul L.; Hadley, Dean R.; Milanovich, Fred P.; Belgrader, Phil; Meyer, Peter L.

2004-03-02

A portable polymerase chain reaction DNA amplification and detection system includes one or more chamber modules. Each module supports a duplex assay of a biological sample. Each module has two parallel interrogation ports with a linear optical system. The system is capable of being handheld.

Tetrahymena in the classroom.

PubMed

Smith, Joshua J; Wiley, Emily A; Cassidy-Hanley, Donna M

2012-01-01

Tetrahymena has been a useful model in basic research in part due to the fact it is easy to grow in culture and exhibits a range of complex processes, all within a single cell. For these same reasons Tetrahymena has shown enormous potential as a teaching tool for fundamental principles of biology at multiple science education levels that can be integrated into K-12 classrooms and undergraduate and graduate college laboratory courses. These Tetrahymena-based teaching modules are inquiry-based experiences that are also effective at teaching scientific concepts, retaining students in science, and exciting students about the scientific process. Two learning communities have been developed that utilize Tetrahymena-based teaching modules. Advancing Secondary Science Education with Tetrahymena (ASSET) and the Ciliate Genomics Consortium (CGC) have developed modules for K-12 students and college-level curriculums, respectively. These modules range from addressing topics in ecology, taxonomy, and environmental toxicity to more advanced concepts in biochemistry, proteomics, bioinformatics, cell biology, and molecular biology. An overview of the current modules and their learning outcomes are discussed, as are assessment, dissemination, and sustainability strategies for K-12 and college-level curriculum. Copyright © 2012 Elsevier Inc. All rights reserved.

Assessing an effective undergraduate module teaching applied bioinformatics to biology students

PubMed Central

2018-01-01

Applied bioinformatics skills are becoming ever more indispensable for biologists, yet incorporation of these skills into the undergraduate biology curriculum is lagging behind, in part due to a lack of instructors willing and able to teach basic bioinformatics in classes that don’t specifically focus on quantitative skill development, such as statistics or computer sciences. To help undergraduate course instructors who themselves did not learn bioinformatics as part of their own education and are hesitant to plunge into teaching big data analysis, a module was developed that is written in plain-enough language, using publicly available computing tools and data, to allow novice instructors to teach next-generation sequence analysis to upper-level undergraduate students. To determine if the module allowed students to develop a better understanding of and appreciation for applied bioinformatics, various tools were developed and employed to assess the impact of the module. This article describes both the module and its assessment. Students found the activity valuable for their education and, in focus group discussions, emphasized that they saw a need for more and earlier instruction of big data analysis as part of the undergraduate biology curriculum. PMID:29324777

Practice makes pretty good: assessment of primary literature reading abilities across multiple large-enrollment biology laboratory courses.

PubMed

Sato, Brian K; Kadandale, Pavan; He, Wenliang; Murata, Paige M N; Latif, Yama; Warschauer, Mark

2014-01-01

Primary literature is essential for scientific communication and is commonly utilized in undergraduate biology education. Despite this, there is often little time spent training our students how to critically analyze a paper. To address this, we introduced a primary literature module in multiple upper-division laboratory courses. In this module, instructors conduct classroom discussions that dissect a paper as researchers do. While previous work has identified classroom interventions that improve primary literature comprehension within a single course, our goal was to determine whether including a scientific paper module in our classes could produce long-term benefits. On the basis of performance in an assessment exam, we found that our module resulted in longitudinal gains, including increased comprehension and critical-thinking abilities in subsequent lab courses. These learning gains were specific to courses utilizing our module, as no longitudinal gains were seen in students who had taken other upper-division labs that lacked extensive primary literature discussion. In addition, we assessed whether performance on our assessment correlated with a variety of factors, including grade point average, course performance, research background, and self-reported confidence in understanding of the article. Furthermore, all of the study conclusions are independent of biology disciplines, as we observe similar trends within each course. © 2014 B. K. Sato et al. CBE—Life Sciences Education © 2014 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).

Growth: How Much is Too Much? Teacher's Guide. Science Module (9th-10th Grade Biology).

ERIC Educational Resources Information Center

Georgia Univ., Athens. Coll. of Education.

This is a teacher's guide for a learning module designed to integrate environmental education into ninth- and tenth-grade chemistry classes. This module and a companion social studies module were pilot tested in Gwinnett County, Georgia in 1975-76. The module is divided into four parts. Part one provides a broad overview of unit content and…

Growth: How Much is Too Much? Student Book. Science Module (9th-10th Grade Biology). Revised Edition.

ERIC Educational Resources Information Center

Georgia Univ., Athens. Coll. of Education.

This learning module is designed to integrate environmental education into ninth- and tenth-grade chemistry classes. This module and a companion social studies module were pilot tested in Gwinnett County, Georgia in 1975-76. The module is divided into four parts. Part one provides a broad overview of unit content and proposes questions to…

BioInt: an integrative biological object-oriented application framework and interpreter.

PubMed

Desai, Sanket; Burra, Prasad

2015-01-01

BioInt, a biological programming application framework and interpreter, is an attempt to equip the researchers with seamless integration, efficient extraction and effortless analysis of the data from various biological databases and algorithms. Based on the type of biological data, algorithms and related functionalities, a biology-specific framework was developed which has nine modules. The modules are a compilation of numerous reusable BioADTs. This software ecosystem containing more than 450 biological objects underneath the interpreter makes it flexible, integrative and comprehensive. Similar to Python, BioInt eliminates the compilation and linking steps cutting the time significantly. The researcher can write the scripts using available BioADTs (following C++ syntax) and execute them interactively or use as a command line application. It has features that enable automation, extension of the framework with new/external BioADTs/libraries and deployment of complex work flows.

The Human Genome Project: Information access, management, and regulation. Final report

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

McInerney, J.D.; Micikas, L.B.

The Human Genome Project is a large, internationally coordinated effort in biological research directed at creating a detailed map of human DNA. This report describes the access of information, management, and regulation of the project. The project led to the development of an instructional module titled The Human Genome Project: Biology, Computers, and Privacy, designed for use in high school biology classes. The module consists of print materials and both Macintosh and Windows versions of related computer software-Appendix A contains a copy of the print materials and discs containing the two versions of the software.

Improving the signal-to-noise ratio in ultrasound-modulated optical tomography by a lock-in amplifier

NASA Astrophysics Data System (ADS)

Zhu, Lili; Wu, Jingping; Lin, Guimin; Hu, Liangjun; Li, Hui

2016-10-01

With high spatial resolution of ultrasonic location and high sensitivity of optical detection, ultrasound-modulated optical tomography (UOT) is a promising noninvasive biological tissue imaging technology. In biological tissue, the ultrasound-modulated light signals are very weak and are overwhelmed by the strong unmodulated light signals. It is a difficulty and key to efficiently pick out the weak modulated light from strong unmodulated light in UOT. Under the effect of an ultrasonic field, the scattering light intensity presents a periodic variation as the ultrasonic frequency changes. So the modulated light signals would be escape from the high unmodulated light signals, when the modulated light signals and the ultrasonic signal are processed cross correlation operation by a lock-in amplifier and without a chopper. Experimental results indicated that the signal-to-noise ratio of UOT is significantly improved by a lock-in amplifier, and the higher the repetition frequency of pulsed ultrasonic wave, the better the signal-to-noise ratio of UOT.

From Saccharomyces cerevisiae to human: The important gene co-expression modules.

PubMed

Liu, Wei; Li, Li; Ye, Hua; Chen, Haiwei; Shen, Weibiao; Zhong, Yuexian; Tian, Tian; He, Huaqin

2017-08-01

Network-based systems biology has become an important method for analyzing high-throughput gene expression data and gene function mining. Yeast has long been a popular model organism for biomedical research. In the current study, a weighted gene co-expression network analysis algorithm was applied to construct a gene co-expression network in Saccharomyces cerevisiae . Seventeen stable gene co-expression modules were detected from 2,814 S. cerevisiae microarray data. Further characterization of these modules with the Database for Annotation, Visualization and Integrated Discovery tool indicated that these modules were associated with certain biological processes, such as heat response, cell cycle, translational regulation, mitochondrion oxidative phosphorylation, amino acid metabolism and autophagy. Hub genes were also screened by intra-modular connectivity. Finally, the module conservation was evaluated in a human disease microarray dataset. Functional modules were identified in budding yeast, some of which are associated with patient survival. The current study provided a paradigm for single cell microorganisms and potentially other organisms.

Recent Progress in the Design and Discovery of RXR Modulators Targeting Alternate Binding Sites of the Receptor.

PubMed

Su, Ying; Zeng, Zhiping; Chen, Ziwen; Xu, Dan; Zhang, Weidong; Zhang, Xiao-Kun

2017-01-01

Retinoid X receptors (RXRs) occupy a central position within the nuclear receptor superfamily. They not only function as important transcriptional factors but also exhibit diverse nongenomic biological activities. The pleiotropic actions of RXRs under both physiological and pathophysiological conditions confer RXRs important drug targets for the treatment of cancer, and metabolic and neurodegenerative diseases. RXR modulators have been studied for the purpose of developing both drug molecules and chemical tools for biological investigation of RXR. Development of RXR modulators has focused on small molecules targeting the canonical ligand-binding pocket. However, accumulating results have demonstrated that there are other binding mechanisms by which small molecules interact with RXR to act as RXR modulators. This review discusses the recent development in the design and discovery of RXR modulators with a focus on those targeting novel binding sites on RXR.

Evolution of functional specialization and division of labor.

PubMed

Rueffler, Claus; Hermisson, Joachim; Wagner, Günter P

2012-02-07

Division of labor among functionally specialized modules occurs at all levels of biological organization in both animals and plants. Well-known examples include the evolution of specialized enzymes after gene duplication, the evolution of specialized cell types, limb diversification in arthropods, and the evolution of specialized colony members in many taxa of marine invertebrates and social insects. Here, we identify conditions favoring the evolution of division of labor by means of a general mathematical model. Our starting point is the assumption that modules contribute to two different biological tasks and that the potential of modules to contribute to these tasks is traded off. Our results are phrased in terms of properties of performance functions that map the phenotype of modules to measures of performance. We show that division of labor is favored by three factors: positional effects that predispose modules for one of the tasks, accelerating performance functions, and synergistic interactions between modules. If modules can be lost or damaged, selection for robustness can counteract selection for functional specialization. To illustrate our theory we apply it to the evolution of specialized enzymes coded by duplicated genes.

Fiber-based polarization-sensitive Mueller matrix optical coherence tomography with continuous source polarization modulation.

PubMed

Jiao, Shuliang; Todorović, Milos; Stoica, George; Wang, Lihong V

2005-09-10

We report on a new configuration of fiber-based polarization-sensitive Mueller matrix optical coherence tomography that permits the acquisition of the round-trip Jones matrix of a biological sample using only one light source and a single depth scan. In this new configuration, a polarization modulator is used in the source arm to continuously modulate the incident polarization state for both the reference and the sample arms. The Jones matrix of the sample can be calculated from the two frequency terms in the two detection channels. The first term is modulated by the carrier frequency, which is determined by the longitudinal scanning mechanism, whereas the other term is modulated by the beat frequency between the carrier frequency and the second harmonic of the modulation frequency of the polarization modulator. One important feature of this system is that, for the first time to our knowledge, the Jones matrix of the sample can be calculated with a single detection channel and a single measurement when diattenuation is negligible. The system was successfully tested by imaging both standard polarization elements and biological samples.

Biologic Modulators in Allergic and Autoinflammatory Diseases

PubMed Central

Broderick, Lori; Tourangeau, Louanne M.; Kavanaugh, Arthur; Wasserman, Stephen I.

2011-01-01

Purpose of review The advent of molecular techniques has resulted in the ability to tailor medications to specific protein targets. This review will emphasize several biological therapies, specifically directed toward cytokine receptors and inhibitors, and their role in the treatment of atopic and autoinflammatory diseases. Recent findings Translational research and the identification of the molecular pathophysiology of diseases have led to more targeted treatment approaches. The biologic modulators, encompassing monoclonal antibodies as cytokine inhibitors, receptor blocking antibodies and new fusion receptors are now being applied to diseases beyond their original application. Summary The expanded use of biological therapies has experienced success in the treatment of numerous disorders, especially in subsets of patients with disease that has been refractory to conventional therapies. PMID:21659854

Photorefractive detection of tagged photons in ultrasound modulated optical tomography of thick biological tissues.

PubMed

Ramaz, F; Forget, B; Atlan, M; Boccara, A C; Gross, M; Delaye, P; Roosen, G

2004-11-01

We present a new and simple method to obtain ultrasound modulated optical tomography images in thick biological tissues with the use of a photorefractive crystal. The technique offers the advantage of spatially adapting the output speckle wavefront by analysing the signal diffracted by the interference pattern between this output field and a reference beam, recorded inside the photorefractive crystal. Averaging out due to random phases of the speckle grains vanishes, and we can use a fast single photodetector to measure the ultrasound modulated optical contrast. This technique offers a promising way to make direct measurements within the decorrelation time scale of living tissues.

Androgens: basic biology and clinical implication.

PubMed

Orwoll, E S

2001-10-01

Although androgens have been considered essential modulators of bone biology in men, recent studies have indicated that estrogen may have an important, if not dominant, role. Nevertheless, there is strong evidence that androgens have independent skeletal actions. Nonaromatizable androgens influence a variety of aspects of bone cell biology and are capable of modulating bone remodeling and bone mass. It appears that androgens are particularly important in the control of periosteal bone formation, an effect that might underlie the gender difference in bone size. Alterations in androgen receptor function affect bone metabolism, and new information suggests that androgens modulate receptor homeostasis. The clinical implications of androgen effects, and how they interact with those of estrogens, are somewhat unclear. It is likely that overall bone homeostasis and gender differences depend on a combination of androgenic and estrogenic actions. Androgens may well provide advantages in the prevention and therapy of metabolic bone disorders in both men and women.

Lateral Hypothalamus GABAergic Neurons Modulate Consummatory Behaviors Regardless of the Caloric Content or Biological Relevance of the Consumed Stimuli.

PubMed

Navarro, Montserrat; Olney, Jeffrey J; Burnham, Nathan W; Mazzone, Christopher M; Lowery-Gionta, Emily G; Pleil, Kristen E; Kash, Thomas L; Thiele, Todd E

2016-05-01

It was recently reported that activation of a subset of lateral hypothalamus (LH) GABAergic neurons induced both appetitive (food-seeking) and consummatory (eating) behaviors in vGat-ires-cre mice, while inhibition or deletion of GABAergic neurons blunted these behaviors. As food and caloric-dense liquid solutions were used, the data reported suggest that these LH GABAergic neurons may modulate behaviors that function to maintain homeostatic caloric balance. Here we report that chemogenetic activation of this GABAergic population in vGat-ires-cre mice increased consummatory behavior directed at any available stimulus, including those entailing calories (food, sucrose, and ethanol), those that do not (saccharin and water), and those lacking biological relevance (wood). Chemogenetic inhibition of these neurons attenuated consummatory behaviors. These data indicate that LH GABAergic neurons modulate consummatory behaviors regardless of the caloric content or biological relevance of the consumed stimuli.

Integrated Modular Teaching of Human Biology for Primary Care Practitioners

ERIC Educational Resources Information Center

Glasgow, Michael S.

1977-01-01

Describes the use of integrated modular teaching of the human biology component of the Health Associate Program at Johns Hopkins University, where the goal is to develop an understanding of the sciences as applied to primary care. Discussion covers the module sequence, the human biology faculty, goals of the human biology faculty, laboratory…

Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging *

PubMed Central

Afornali, Alessandro; de Vecchi, Rodrigo; Stuart, Rodrigo Makowiecky; Dieamant, Gustavo; de Oliveira, Luciana Lima; Brohem, Carla Abdo; Feferman, Israel Henrique Stokfisz; Fabrício, Lincoln Helder Zambaldi; Lorencini, Márcio

2013-01-01

BACKGROUND The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly. PMID:24474102

THD-Module Extractor: An Application for CEN Module Extraction and Interesting Gene Identification for Alzheimer's Disease.

PubMed

Kakati, Tulika; Kashyap, Hirak; Bhattacharyya, Dhruba K

2016-11-30

There exist many tools and methods for construction of co-expression network from gene expression data and for extraction of densely connected gene modules. In this paper, a method is introduced to construct co-expression network and to extract co-expressed modules having high biological significance. The proposed method has been validated on several well known microarray datasets extracted from a diverse set of species, using statistical measures, such as p and q values. The modules obtained in these studies are found to be biologically significant based on Gene Ontology enrichment analysis, pathway analysis, and KEGG enrichment analysis. Further, the method was applied on an Alzheimer's disease dataset and some interesting genes are found, which have high semantic similarity among them, but are not significantly correlated in terms of expression similarity. Some of these interesting genes, such as MAPT, CASP2, and PSEN2, are linked with important aspects of Alzheimer's disease, such as dementia, increase cell death, and deposition of amyloid-beta proteins in Alzheimer's disease brains. The biological pathways associated with Alzheimer's disease, such as, Wnt signaling, Apoptosis, p53 signaling, and Notch signaling, incorporate these interesting genes. The proposed method is evaluated in regard to existing literature.

Enhancing biological relevance of a weighted gene co-expression network for functional module identification.

PubMed

Prom-On, Santitham; Chanthaphan, Atthawut; Chan, Jonathan Hoyin; Meechai, Asawin

2011-02-01

Relationships among gene expression levels may be associated with the mechanisms of the disease. While identifying a direct association such as a difference in expression levels between case and control groups links genes to disease mechanisms, uncovering an indirect association in the form of a network structure may help reveal the underlying functional module associated with the disease under scrutiny. This paper presents a method to improve the biological relevance in functional module identification from the gene expression microarray data by enhancing the structure of a weighted gene co-expression network using minimum spanning tree. The enhanced network, which is called a backbone network, contains only the essential structural information to represent the gene co-expression network. The entire backbone network is decoupled into a number of coherent sub-networks, and then the functional modules are reconstructed from these sub-networks to ensure minimum redundancy. The method was tested with a simulated gene expression dataset and case-control expression datasets of autism spectrum disorder and colorectal cancer studies. The results indicate that the proposed method can accurately identify clusters in the simulated dataset, and the functional modules of the backbone network are more biologically relevant than those obtained from the original approach.

THD-Module Extractor: An Application for CEN Module Extraction and Interesting Gene Identification for Alzheimer’s Disease

PubMed Central

Kakati, Tulika; Kashyap, Hirak; Bhattacharyya, Dhruba K.

2016-01-01

There exist many tools and methods for construction of co-expression network from gene expression data and for extraction of densely connected gene modules. In this paper, a method is introduced to construct co-expression network and to extract co-expressed modules having high biological significance. The proposed method has been validated on several well known microarray datasets extracted from a diverse set of species, using statistical measures, such as p and q values. The modules obtained in these studies are found to be biologically significant based on Gene Ontology enrichment analysis, pathway analysis, and KEGG enrichment analysis. Further, the method was applied on an Alzheimer’s disease dataset and some interesting genes are found, which have high semantic similarity among them, but are not significantly correlated in terms of expression similarity. Some of these interesting genes, such as MAPT, CASP2, and PSEN2, are linked with important aspects of Alzheimer’s disease, such as dementia, increase cell death, and deposition of amyloid-beta proteins in Alzheimer’s disease brains. The biological pathways associated with Alzheimer’s disease, such as, Wnt signaling, Apoptosis, p53 signaling, and Notch signaling, incorporate these interesting genes. The proposed method is evaluated in regard to existing literature. PMID:27901073

Health Instruction Packages: Basic Sciences.

ERIC Educational Resources Information Center

Cathey, Barbara; And Others

Text, illustrations, and exercises are utilized in a set of nine learning modules designed to instruct nursing and allied health students in a variety of biological topics. The first module, by Barbara Cathey, discusses cell growth and the proliferation of cells in benign and malignant tumors. The second module, by Eugene Volz, describes the…

The multiscale backbone of the human phenotype network based on biological pathways.

PubMed

Darabos, Christian; White, Marquitta J; Graham, Britney E; Leung, Derek N; Williams, Scott M; Moore, Jason H

2014-01-25

Networks are commonly used to represent and analyze large and complex systems of interacting elements. In systems biology, human disease networks show interactions between disorders sharing common genetic background. We built pathway-based human phenotype network (PHPN) of over 800 physical attributes, diseases, and behavioral traits; based on about 2,300 genes and 1,200 biological pathways. Using GWAS phenotype-to-genes associations, and pathway data from Reactome, we connect human traits based on the common patterns of human biological pathways, detecting more pleiotropic effects, and expanding previous studies from a gene-centric approach to that of shared cell-processes. The resulting network has a heavily right-skewed degree distribution, placing it in the scale-free region of the network topologies spectrum. We extract the multi-scale information backbone of the PHPN based on the local densities of the network and discarding weak connection. Using a standard community detection algorithm, we construct phenotype modules of similar traits without applying expert biological knowledge. These modules can be assimilated to the disease classes. However, we are able to classify phenotypes according to shared biology, and not arbitrary disease classes. We present examples of expected clinical connections identified by PHPN as proof of principle. We unveil a previously uncharacterized connection between phenotype modules and discuss potential mechanistic connections that are obvious only in retrospect. The PHPN shows tremendous potential to become a useful tool both in the unveiling of the diseases' common biology, and in the elaboration of diagnosis and treatments.

Reconstruction of gene regulatory modules from RNA silencing of IFN-α modulators: experimental set-up and inference method.

PubMed

Grassi, Angela; Di Camillo, Barbara; Ciccarese, Francesco; Agnusdei, Valentina; Zanovello, Paola; Amadori, Alberto; Finesso, Lorenzo; Indraccolo, Stefano; Toffolo, Gianna Maria

2016-03-12

Inference of gene regulation from expression data may help to unravel regulatory mechanisms involved in complex diseases or in the action of specific drugs. A challenging task for many researchers working in the field of systems biology is to build up an experiment with a limited budget and produce a dataset suitable to reconstruct putative regulatory modules worth of biological validation. Here, we focus on small-scale gene expression screens and we introduce a novel experimental set-up and a customized method of analysis to make inference on regulatory modules starting from genetic perturbation data, e.g. knockdown and overexpression data. To illustrate the utility of our strategy, it was applied to produce and analyze a dataset of quantitative real-time RT-PCR data, in which interferon-α (IFN-α) transcriptional response in endothelial cells is investigated by RNA silencing of two candidate IFN-α modulators, STAT1 and IFIH1. A putative regulatory module was reconstructed by our method, revealing an intriguing feed-forward loop, in which STAT1 regulates IFIH1 and they both negatively regulate IFNAR1. STAT1 regulation on IFNAR1 was object of experimental validation at the protein level. Detailed description of the experimental set-up and of the analysis procedure is reported, with the intent to be of inspiration for other scientists who want to realize similar experiments to reconstruct gene regulatory modules starting from perturbations of possible regulators. Application of our approach to the study of IFN-α transcriptional response modulators in endothelial cells has led to many interesting novel findings and new biological hypotheses worth of validation.

CytoCluster: A Cytoscape Plugin for Cluster Analysis and Visualization of Biological Networks.

PubMed

Li, Min; Li, Dongyan; Tang, Yu; Wu, Fangxiang; Wang, Jianxin

2017-08-31

Nowadays, cluster analysis of biological networks has become one of the most important approaches to identifying functional modules as well as predicting protein complexes and network biomarkers. Furthermore, the visualization of clustering results is crucial to display the structure of biological networks. Here we present CytoCluster, a cytoscape plugin integrating six clustering algorithms, HC-PIN (Hierarchical Clustering algorithm in Protein Interaction Networks), OH-PIN (identifying Overlapping and Hierarchical modules in Protein Interaction Networks), IPCA (Identifying Protein Complex Algorithm), ClusterONE (Clustering with Overlapping Neighborhood Expansion), DCU (Detecting Complexes based on Uncertain graph model), IPC-MCE (Identifying Protein Complexes based on Maximal Complex Extension), and BinGO (the Biological networks Gene Ontology) function. Users can select different clustering algorithms according to their requirements. The main function of these six clustering algorithms is to detect protein complexes or functional modules. In addition, BinGO is used to determine which Gene Ontology (GO) categories are statistically overrepresented in a set of genes or a subgraph of a biological network. CytoCluster can be easily expanded, so that more clustering algorithms and functions can be added to this plugin. Since it was created in July 2013, CytoCluster has been downloaded more than 9700 times in the Cytoscape App store and has already been applied to the analysis of different biological networks. CytoCluster is available from http://apps.cytoscape.org/apps/cytocluster.

CytoCluster: A Cytoscape Plugin for Cluster Analysis and Visualization of Biological Networks

PubMed Central

Li, Min; Li, Dongyan; Tang, Yu; Wang, Jianxin

2017-01-01

Nowadays, cluster analysis of biological networks has become one of the most important approaches to identifying functional modules as well as predicting protein complexes and network biomarkers. Furthermore, the visualization of clustering results is crucial to display the structure of biological networks. Here we present CytoCluster, a cytoscape plugin integrating six clustering algorithms, HC-PIN (Hierarchical Clustering algorithm in Protein Interaction Networks), OH-PIN (identifying Overlapping and Hierarchical modules in Protein Interaction Networks), IPCA (Identifying Protein Complex Algorithm), ClusterONE (Clustering with Overlapping Neighborhood Expansion), DCU (Detecting Complexes based on Uncertain graph model), IPC-MCE (Identifying Protein Complexes based on Maximal Complex Extension), and BinGO (the Biological networks Gene Ontology) function. Users can select different clustering algorithms according to their requirements. The main function of these six clustering algorithms is to detect protein complexes or functional modules. In addition, BinGO is used to determine which Gene Ontology (GO) categories are statistically overrepresented in a set of genes or a subgraph of a biological network. CytoCluster can be easily expanded, so that more clustering algorithms and functions can be added to this plugin. Since it was created in July 2013, CytoCluster has been downloaded more than 9700 times in the Cytoscape App store and has already been applied to the analysis of different biological networks. CytoCluster is available from http://apps.cytoscape.org/apps/cytocluster. PMID:28858211

A Bioethics Course for Biology and Science Education Students.

ERIC Educational Resources Information Center

Bryant, John; la Velle, Linda Baggott

2003-01-01

Points out the importance of awareness among biologists and biology teachers of the ethical and social implications of their work. Describes the bioethics module established at the University of Exeter mainly targeting students majoring in biology and science education. (Contains 18 references.) (Author/YDS)

Monitoring of biological markers indicative of doping: the athlete biological passport.

PubMed

Saugy, Martial; Lundby, Carsten; Robinson, Neil

2014-05-01

The athlete biological passport (ABP) was recently implemented in anti-doping work and is based on the individual and longitudinal monitoring of haematological or urine markers. These may be influenced by illicit procedures performed by some athletes with the intent to improve exercise performance. Hence the ABP is a valuable tool in the fight against doping. Actually, the passport has been defined as an individual and longitudinal observation of markers. These markers need to belong to the biological cascade influenced by the application of forbidden hormones or more generally, affected by biological manipulations which can improve the performance of the athlete. So far, the haematological and steroid profile modules of the ABP have been implemented in major sport organisations, and a further module is under development. The individual and longitudinal monitoring of some blood and urine markers are of interest, because the intraindividual variability is lower than the corresponding interindividual variability. Among the key prerequisites for the implementation of the ABP is its prospect to resist to the legal and scientific challenges. The ABP should be implemented in the most transparent way and with the necessary independence between planning, interpretation and result management of the passport. To ensure this, the Athlete Passport Management Unit (APMU) was developed and the WADA implemented different technical documents associated to the passport. This was carried out to ensure the correct implementation of a profile which can also stand the challenge of any scientific or legal criticism. This goal can be reached only by following strictly important steps in the chain of production of the results and in the management of the interpretation of the passport. Various technical documents have been then associated to the guidelines which correspond to the requirements for passport operation. The ABP has been completed very recently by the steroid profile module. As for the haematological module, individual and longitudinal monitoring have been applied and the interpretation cascade is also managed by a specific APMU in a similar way as applied in the haematological module. Thus, after exclusion of any possible pathology, specific variation from the individual norms will be then considered as a potential misuse of hormones or other modulators to enhance performance.

BinTree Seeking: A Novel Approach to Mine Both Bi-Sparse and Cohesive Modules in Protein Interaction Networks

PubMed Central

Shen, Hong-Bin

2011-01-01

Modern science of networks has brought significant advances to our understanding of complex systems biology. As a representative model of systems biology, Protein Interaction Networks (PINs) are characterized by a remarkable modular structures, reflecting functional associations between their components. Many methods were proposed to capture cohesive modules so that there is a higher density of edges within modules than those across them. Recent studies reveal that cohesively interacting modules of proteins is not a universal organizing principle in PINs, which has opened up new avenues for revisiting functional modules in PINs. In this paper, functional clusters in PINs are found to be able to form unorthodox structures defined as bi-sparse module. In contrast to the traditional cohesive module, the nodes in the bi-sparse module are sparsely connected internally and densely connected with other bi-sparse or cohesive modules. We present a novel protocol called the BinTree Seeking (BTS) for mining both bi-sparse and cohesive modules in PINs based on Edge Density of Module (EDM) and matrix theory. BTS detects modules by depicting links and nodes rather than nodes alone and its derivation procedure is totally performed on adjacency matrix of networks. The number of modules in a PIN can be automatically determined in the proposed BTS approach. BTS is tested on three real PINs and the results demonstrate that functional modules in PINs are not dominantly cohesive but can be sparse. BTS software and the supporting information are available at: www.csbio.sjtu.edu.cn/bioinf/BTS/. PMID:22140454

Space biology initiative program definition review. Trade study 6: Space Station Freedom/spacelab modules compatibility

NASA Technical Reports Server (NTRS)

Jackson, L. Neal; Crenshaw, John, Sr.; Davidson, William L.; Blacknall, Carolyn; Bilodeau, James W.; Stoval, J. Michael; Sutton, Terry

1989-01-01

The differences in rack requirements for Spacelab, the Shuttle Orbiter, and the United States (U.S.) laboratory module, European Space Agency (ESA) Columbus module, and the Japanese Experiment Module (JEM) of Space Station Freedom are identified. The feasibility of designing standardized mechanical, structural, electrical, data, video, thermal, and fluid interfaces to allow space flight hardware designed for use in the U.S. laboratory module to be used in other locations is assessed.

Teaching High School Chemistry in the Context of Pharmacology Helps Both Teachers and Students Learn

PubMed Central

Schwartz-Bloom, Rochelle D.; Halpin, Myra J.; Reiter, Jerome P.

2014-01-01

Few studies demonstrate the impact of teaching chemistry embedded in a context that has relevance to high school students. We build upon our prior work showing that pharmacology topics (i.e., drugs), which are inherently interesting to high school students, provide a useful context for teaching chemistry and biology. In those studies, teachers were provided professional development for the Pharmacology Education Partnership (PEP) in an onsite venue (either five-day or one-day workshop). Given financial difficulties to travel, teachers have asked for alternatives for professional development. Thus, we developed the same PEP training workshop using a distance learning (DL) (two-way live video) approach. In this way, 121 chemistry and biology teachers participated in the DL workshops to learn how to incorporate the PEP modules into their teaching. They field-tested the modules over the year in high school chemistry and biology classes. Teacher knowledge of chemistry and biology increased significantly after the workshop and was maintained for at least a year. Their students (N = 2309) demonstrated a significant increase in knowledge of chemistry and biology concepts, with higher scores as the number of modules used increased. The increase in both teacher and student knowledge in these subjects was similar to that found previously when teachers were provided with onsite professional development. PMID:24882881

Black pepper (Piper nigrum) essential oil demonstrates tissue remodeling and metabolism modulating potential in human cells.

PubMed

Han, Xuesheng; Beaumont, Cody; Rodriguez, Damian; Bahr, Tyler

2018-05-17

Very few studies have investigated the biological activities of black pepper essential oil (BPEO) in human cells. Therefore, in the current study, we examined the biological activities of BPEO in cytokine-stimulated human dermal fibroblasts by analyzing the levels of 17 important protein biomarkers pertinent to inflammation and tissue remodeling. BPEO exhibited significant antiproliferative activity in these skin cells and significantly inhibited the production of Collagen I, Collagen III, and plasminogen activator inhibitor 1. In addition, we studied the effect of BPEO on the regulation of genome-wide expression and found that BPEO diversely modulated global gene expression. Further analysis showed that BPEO affected many important genes and signaling pathways closely related to metabolism, inflammation, tissue remodeling, and cancer signaling. This study is the first to provide evidence of the biological activities of BPEO in human dermal fibroblasts. The data suggest that BPEO possesses promising potential to modulate the biological processes of tissue remodeling, wound healing, and metabolism. Although further research is required, BPEO appears to be a good therapeutic candidate for a variety of health conditions including wound care and metabolic diseases. Research into the biological and pharmacological mechanisms of action of BPEO and its major active constituents is recommended. Copyright © 2018 John Wiley & Sons, Ltd.

svdPPCS: an effective singular value decomposition-based method for conserved and divergent co-expression gene module identification.

PubMed

Zhang, Wensheng; Edwards, Andrea; Fan, Wei; Zhu, Dongxiao; Zhang, Kun

2010-06-22

Comparative analysis of gene expression profiling of multiple biological categories, such as different species of organisms or different kinds of tissue, promises to enhance the fundamental understanding of the universality as well as the specialization of mechanisms and related biological themes. Grouping genes with a similar expression pattern or exhibiting co-expression together is a starting point in understanding and analyzing gene expression data. In recent literature, gene module level analysis is advocated in order to understand biological network design and system behaviors in disease and life processes; however, practical difficulties often lie in the implementation of existing methods. Using the singular value decomposition (SVD) technique, we developed a new computational tool, named svdPPCS (SVD-based Pattern Pairing and Chart Splitting), to identify conserved and divergent co-expression modules of two sets of microarray experiments. In the proposed methods, gene modules are identified by splitting the two-way chart coordinated with a pair of left singular vectors factorized from the gene expression matrices of the two biological categories. Importantly, the cutoffs are determined by a data-driven algorithm using the well-defined statistic, SVD-p. The implementation was illustrated on two time series microarray data sets generated from the samples of accessory gland (ACG) and malpighian tubule (MT) tissues of the line W118 of M. drosophila. Two conserved modules and six divergent modules, each of which has a unique characteristic profile across tissue kinds and aging processes, were identified. The number of genes contained in these models ranged from five to a few hundred. Three to over a hundred GO terms were over-represented in individual modules with FDR < 0.1. One divergent module suggested the tissue-specific relationship between the expressions of mitochondrion-related genes and the aging process. This finding, together with others, may be of biological significance. The validity of the proposed SVD-based method was further verified by a simulation study, as well as the comparisons with regression analysis and cubic spline regression analysis plus PAM based clustering. svdPPCS is a novel computational tool for the comparative analysis of transcriptional profiling. It especially fits the comparison of time series data of related organisms or different tissues of the same organism under equivalent or similar experimental conditions. The general scheme can be directly extended to the comparisons of multiple data sets. It also can be applied to the integration of data sets from different platforms and of different sources.

Design and evaluation of a digital module with guided peer feedback for student learning biotechnology and molecular life sciences, attitudinal change, and satisfaction.

PubMed

Noroozi, Omid; Mulder, Martin

2017-01-02

This study aims to investigate the impacts of a digital learning module with guided peer feedback on students' domain-specific knowledge gain and their attitudinal change in the field of biotechnology and molecular life sciences. The extent to which the use of this module is appreciated by students is studied as well. A pre-test, post-test design was used with 203 students who were randomly assigned to groups of three. They were asked to work on the digital module with the aim of exploring various perspectives, and the "pros and cons" on the topic of "Genetically Modified Organisms (GMOs)." The results suggest that the module can be used to foster students' domain-specific knowledge gain and their attitudinal change. Furthermore, the module was evaluated positively in terms of students' motivation and satisfaction with the learning experiences. © 2016 by The International Union of Biochemistry and Molecular Biology, 45(1):31-39, 2017. © 2016 The International Union of Biochemistry and Molecular Biology.

Characterization of drug-induced transcriptional modules: towards drug repositioning and functional understanding

PubMed Central

Iskar, Murat; Zeller, Georg; Blattmann, Peter; Campillos, Monica; Kuhn, Michael; Kaminska, Katarzyna H; Runz, Heiko; Gavin, Anne-Claude; Pepperkok, Rainer; van Noort, Vera; Bork, Peer

2013-01-01

In pharmacology, it is crucial to understand the complex biological responses that drugs elicit in the human organism and how well they can be inferred from model organisms. We therefore identified a large set of drug-induced transcriptional modules from genome-wide microarray data of drug-treated human cell lines and rat liver, and first characterized their conservation. Over 70% of these modules were common for multiple cell lines and 15% were conserved between the human in vitro and the rat in vivo system. We then illustrate the utility of conserved and cell-type-specific drug-induced modules by predicting and experimentally validating (i) gene functions, e.g., 10 novel regulators of cellular cholesterol homeostasis and (ii) new mechanisms of action for existing drugs, thereby providing a starting point for drug repositioning, e.g., novel cell cycle inhibitors and new modulators of α-adrenergic receptor, peroxisome proliferator-activated receptor and estrogen receptor. Taken together, the identified modules reveal the conservation of transcriptional responses towards drugs across cell types and organisms, and improve our understanding of both the molecular basis of drug action and human biology. PMID:23632384

BicPAMS: software for biological data analysis with pattern-based biclustering.

PubMed

Henriques, Rui; Ferreira, Francisco L; Madeira, Sara C

2017-02-02

Biclustering has been largely applied for the unsupervised analysis of biological data, being recognised today as a key technique to discover putative modules in both expression data (subsets of genes correlated in subsets of conditions) and network data (groups of coherently interconnected biological entities). However, given its computational complexity, only recent breakthroughs on pattern-based biclustering enabled efficient searches without the restrictions that state-of-the-art biclustering algorithms place on the structure and homogeneity of biclusters. As a result, pattern-based biclustering provides the unprecedented opportunity to discover non-trivial yet meaningful biological modules with putative functions, whose coherency and tolerance to noise can be tuned and made problem-specific. To enable the effective use of pattern-based biclustering by the scientific community, we developed BicPAMS (Biclustering based on PAttern Mining Software), a software that: 1) makes available state-of-the-art pattern-based biclustering algorithms (BicPAM (Henriques and Madeira, Alg Mol Biol 9:27, 2014), BicNET (Henriques and Madeira, Alg Mol Biol 11:23, 2016), BicSPAM (Henriques and Madeira, BMC Bioinforma 15:130, 2014), BiC2PAM (Henriques and Madeira, Alg Mol Biol 11:1-30, 2016), BiP (Henriques and Madeira, IEEE/ACM Trans Comput Biol Bioinforma, 2015), DeBi (Serin and Vingron, AMB 6:1-12, 2011) and BiModule (Okada et al., IPSJ Trans Bioinf 48(SIG5):39-48, 2007)); 2) consistently integrates their dispersed contributions; 3) further explores additional accuracy and efficiency gains; and 4) makes available graphical and application programming interfaces. Results on both synthetic and real data confirm the relevance of BicPAMS for biological data analysis, highlighting its essential role for the discovery of putative modules with non-trivial yet biologically significant functions from expression and network data. BicPAMS is the first biclustering tool offering the possibility to: 1) parametrically customize the structure, coherency and quality of biclusters; 2) analyze large-scale biological networks; and 3) tackle the restrictive assumptions placed by state-of-the-art biclustering algorithms. These contributions are shown to be key for an adequate, complete and user-assisted unsupervised analysis of biological data. BicPAMS and its tutorial available in http://www.bicpams.com .

FamNet: A Framework to Identify Multiplied Modules Driving Pathway Expansion in Plants1

PubMed Central

Tohge, Takayuki; Klie, Sebastian; Fernie, Alisdair R.

2016-01-01

Gene duplications generate new genes that can acquire similar but often diversified functions. Recent studies of gene coexpression networks have indicated that, not only genes, but also pathways can be multiplied and diversified to perform related functions in different parts of an organism. Identification of such diversified pathways, or modules, is needed to expand our knowledge of biological processes in plants and to understand how biological functions evolve. However, systematic explorations of modules remain scarce, and no user-friendly platform to identify them exists. We have established a statistical framework to identify modules and show that approximately one-third of the genes of a plant’s genome participate in hundreds of multiplied modules. Using this framework as a basis, we implemented a platform that can explore and visualize multiplied modules in coexpression networks of eight plant species. To validate the usefulness of the platform, we identified and functionally characterized pollen- and root-specific cell wall modules that multiplied to confer tip growth in pollen tubes and root hairs, respectively. Furthermore, we identified multiplied modules involved in secondary metabolite synthesis and corroborated them by metabolite profiling of tobacco (Nicotiana tabacum) tissues. The interactive platform, referred to as FamNet, is available at http://www.gene2function.de/famnet.html. PMID:26754669

Space Shuttle Projects

NASA Image and Video Library

1995-11-01

This is a view of the Russian Mir Space Station photographed by a crewmember of the second Shuttle/Mir docking mission, STS-74. The image shows: top - Progress supply vehicle, Kvant-1 module, and the Core module; middle left - Spektr module; middle center - Kristall module and Docking module; middle right - Kvant-2 module; and bottom - Soyuz. The Progress was an unmarned, automated version of the Soyuz crew transfer vehicle, designed to resupply the Mir. The Kvant-1 provided research in the physics of galaxies, quasars, and neutron stars by measuring electromagnetic spectra and x-ray emissions. The Core module served as the heart of the space station and contained the primary living and working areas, life support, and power, as well as the main computer, communications, and control equipment. The Spektr module provided Earth observation. It also supported research into biotechnology, life sciences, materials science, and space technologies. American astronauts used the Spektr as their living quarters. A main purpose of the Kristall module was to develop biological and materials production technologies in the space environment. The Docking module made it possible for the Space Shuttle to dock easily with the Mir. Kvant-2 was a scientific and airlock module, providing biological research, Earth observations, and EVA (extravehicular activity) capability. The Soyuz typically ferried three crewmembers to and from the Mir. The journey of the 15-year-old Russian Mir Space Station ended March 23, 2001, as the Mir re-entered the Earth's atmosphere and fell into the south Pacific Ocean.

Prepare, Do, Review: A skills-based approach for laboratory practical classes in biochemistry and molecular biology.

PubMed

Arthur, Peter; Ludwig, Martha; Castelli, Joane; Kirkwood, Paul; Attwood, Paul

2016-05-06

A new laboratory practical system is described which is comprised of a number of laboratory practical modules, each based around a particular technique or set of techniques, related to the theory part of the course but not designed to be dependent on it. Each module comprises an online recorded pre-lab lecture, the laboratory practical itself and a post-lab session in which students make oral presentations on different aspects of the practical. Each part of the module is assessed with the aim of providing rapid feedback to staff and students. Each laboratory practical is the responsibility of a single staff member and through this "ownership," continual review and updating is promoted. Examples of changes made by staff to modules as a result of student feedback are detailed. A survey of students who had experienced both the old-style laboratory course and the new one provided evidence of increased satisfaction with the new program. The assessment of acquired shills in the new program showed that it was much more effective than the old course. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:276-287, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

Metacognition Modules: A Scaffolded Series of Online Assignments Designed to Improve Students’ Study Skills†

PubMed Central

Cardinale, Jean A.; Johnson, Bethany C.

2017-01-01

Many first-year biology students begin college with high aspirations but limited skills in terms of those needed for their success. Teachers are increasingly focused on students’ lack of metacognitive awareness combined with students’ inability to self-regulate learning behaviors. To address this need, we have designed a series of out-of-class assignments to provide explicit instruction on memory and learning. Our metacognition modules consist of six video assignments with reflective journaling prompts, allowing students to explore the relationship between the learning cycle, neuroplasticity, memory function, expert and novice thinking, and effective study strategies. By setting lessons on improving study behavior within a biological context, we help students grasp the reason for changing their behavior based on an understanding of biological functions and their application to learning. Students who complete these scaffolded journaling assignments show a shift toward a growth mindset and a consistent ability to evaluate the efficacy of their own study behaviors. In this article, we discuss the modules and student assignments, as well as provide in depth support for faculty who wish to adopt the modules for their own courses. PMID:28904648

Finding pathway-modulating genes from a novel Ontology Fingerprint-derived gene network.

PubMed

Qin, Tingting; Matmati, Nabil; Tsoi, Lam C; Mohanty, Bidyut K; Gao, Nan; Tang, Jijun; Lawson, Andrew B; Hannun, Yusuf A; Zheng, W Jim

2014-10-01

To enhance our knowledge regarding biological pathway regulation, we took an integrated approach, using the biomedical literature, ontologies, network analyses and experimental investigation to infer novel genes that could modulate biological pathways. We first constructed a novel gene network via a pairwise comparison of all yeast genes' Ontology Fingerprints--a set of Gene Ontology terms overrepresented in the PubMed abstracts linked to a gene along with those terms' corresponding enrichment P-values. The network was further refined using a Bayesian hierarchical model to identify novel genes that could potentially influence the pathway activities. We applied this method to the sphingolipid pathway in yeast and found that many top-ranked genes indeed displayed altered sphingolipid pathway functions, initially measured by their sensitivity to myriocin, an inhibitor of de novo sphingolipid biosynthesis. Further experiments confirmed the modulation of the sphingolipid pathway by one of these genes, PFA4, encoding a palmitoyl transferase. Comparative analysis showed that few of these novel genes could be discovered by other existing methods. Our novel gene network provides a unique and comprehensive resource to study pathway modulations and systems biology in general. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Finding pathway-modulating genes from a novel Ontology Fingerprint-derived gene network

PubMed Central

Qin, Tingting; Matmati, Nabil; Tsoi, Lam C.; Mohanty, Bidyut K.; Gao, Nan; Tang, Jijun; Lawson, Andrew B.; Hannun, Yusuf A.; Zheng, W. Jim

2014-01-01

To enhance our knowledge regarding biological pathway regulation, we took an integrated approach, using the biomedical literature, ontologies, network analyses and experimental investigation to infer novel genes that could modulate biological pathways. We first constructed a novel gene network via a pairwise comparison of all yeast genes’ Ontology Fingerprints—a set of Gene Ontology terms overrepresented in the PubMed abstracts linked to a gene along with those terms’ corresponding enrichment P-values. The network was further refined using a Bayesian hierarchical model to identify novel genes that could potentially influence the pathway activities. We applied this method to the sphingolipid pathway in yeast and found that many top-ranked genes indeed displayed altered sphingolipid pathway functions, initially measured by their sensitivity to myriocin, an inhibitor of de novo sphingolipid biosynthesis. Further experiments confirmed the modulation of the sphingolipid pathway by one of these genes, PFA4, encoding a palmitoyl transferase. Comparative analysis showed that few of these novel genes could be discovered by other existing methods. Our novel gene network provides a unique and comprehensive resource to study pathway modulations and systems biology in general. PMID:25063300

The human heart and the circulatory system as an interesting interdisciplinary topic in lessons of physics and biology

NASA Astrophysics Data System (ADS)

Volná, M.; Látal, F.; Kubínek, R.; Richterek, L.

2014-01-01

Many topics which are closely related can be found in the national curriculum of the Czech Republic for physics and biology. One of them is the heart and the circulatory system in the human body. This topic was examined cross curriculum, a teaching module was created and the topic was chosen for our research. The task was to determine if the students of bachelor study are aware of connections between physics and biology within this topic and whether we can help them effectively to describe the corresponding physics phenomena in the human body connected, for example, with a heart attack or with the measurement of blood pressure. In this paper, the heart and the circulatory system are presented as suitable topics for an interdisciplinary teaching module which includes both theoretical and experimental parts. The module was evaluated by a group of first-year undergraduate students of physics at the Faculty of Science, Palacký University. The acquired knowledge was compared with another control group through a test. The highest efficiency of the module was evaluated on the basis of questions that covered the calculation problems.

Using a Module-based Laboratory To Incorporate Inquiry into a Large Cell Biology Course

PubMed Central

2005-01-01

Because cell biology has rapidly increased in breadth and depth, instructors are challenged not only to provide undergraduate science students with a strong, up-to-date foundation of knowledge, but also to engage them in the scientific process. To these ends, revision of the Cell Biology Lab course at the University of Wisconsin–La Crosse was undertaken to allow student involvement in experimental design, emphasize data collection and analysis, make connections to the “big picture,” and increase student interest in the field. Multiweek laboratory modules were developed as a method to establish an inquiry-based learning environment. Each module utilizes relevant techniques to investigate one or more questions within the context of a fictional story, and there is a progression during the semester from more instructor-guided to more open-ended student investigation. An assessment tool was developed to evaluate student attitudes regarding their lab experience. Analysis of five semesters of data strongly supports the module format as a successful model for inquiry education by increasing student interest and improving attitude toward learning. In addition, student performance on inquiry-based assignments improved over the course of each semester, suggesting an improvement in inquiry-related skills. PMID:16220145

Biology Modules for the Visually Handicapped.

ERIC Educational Resources Information Center

Allan, Douglas M.

The instructional materials presented and described in this document were prepared as part of a project to develop enrichment materials for visually impaired biology students. A wide range of biology topics are presented, including most subjects covered in a one-semester course for nonmajors. Typewritten handouts, duplicating the content of…

Module-based multiscale simulation of angiogenesis in skeletal muscle

PubMed Central

2011-01-01

Background Mathematical modeling of angiogenesis has been gaining momentum as a means to shed new light on the biological complexity underlying blood vessel growth. A variety of computational models have been developed, each focusing on different aspects of the angiogenesis process and occurring at different biological scales, ranging from the molecular to the tissue levels. Integration of models at different scales is a challenging and currently unsolved problem. Results We present an object-oriented module-based computational integration strategy to build a multiscale model of angiogenesis that links currently available models. As an example case, we use this approach to integrate modules representing microvascular blood flow, oxygen transport, vascular endothelial growth factor transport and endothelial cell behavior (sensing, migration and proliferation). Modeling methodologies in these modules include algebraic equations, partial differential equations and agent-based models with complex logical rules. We apply this integrated model to simulate exercise-induced angiogenesis in skeletal muscle. The simulation results compare capillary growth patterns between different exercise conditions for a single bout of exercise. Results demonstrate how the computational infrastructure can effectively integrate multiple modules by coordinating their connectivity and data exchange. Model parameterization offers simulation flexibility and a platform for performing sensitivity analysis. Conclusions This systems biology strategy can be applied to larger scale integration of computational models of angiogenesis in skeletal muscle, or other complex processes in other tissues under physiological and pathological conditions. PMID:21463529

A machine-learned analysis of human gene polymorphisms modulating persisting pain points at major roles of neuroimmune processes.

PubMed

Kringel, Dario; Lippmann, Catharina; Parnham, Michael J; Kalso, Eija; Ultsch, Alfred; Lötsch, Jörn

2018-06-19

Human genetic research has implicated functional variants of more than one hundred genes in the modulation of persisting pain. Artificial intelligence and machine learning techniques may combine this knowledge with results of genetic research gathered in any context, which permits the identification of the key biological processes involved in chronic sensitization to pain. Based on published evidence, a set of 110 genes carrying variants reported to be associated with modulation of the clinical phenotype of persisting pain in eight different clinical settings was submitted to unsupervised machine-learning aimed at functional clustering. Subsequently, a mathematically supported subset of genes, comprising those most consistently involved in persisting pain, was analyzed by means of computational functional genomics in the Gene Ontology knowledgebase. Clustering of genes with evidence for a modulation of persisting pain elucidated a functionally heterogeneous set. The situation cleared when the focus was narrowed to a genetic modulation consistently observed throughout several clinical settings. On this basis, two groups of biological processes, the immune system and nitric oxide signaling, emerged as major players in sensitization to persisting pain, which is biologically highly plausible and in agreement with other lines of pain research. The present computational functional genomics-based approach provided a computational systems-biology perspective on chronic sensitization to pain. Human genetic control of persisting pain points to the immune system as a source of potential future targets for drugs directed against persisting pain. Contemporary machine-learned methods provide innovative approaches to knowledge discovery from previous evidence. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Low Fidelity Imitation of Atypical Biological Kinematics in Autism Spectrum Disorders Is Modulated by Self-Generated Selective Attention.

PubMed

Hayes, Spencer J; Andrew, Matthew; Elliott, Digby; Gowen, Emma; Bennett, Simon J

2016-02-01

We examined whether adults with autism had difficulty imitating atypical biological kinematics. To reduce the impact that higher-order processes have on imitation we used a non-human agent model to control social attention, and removed end-state target goals in half of the trials to minimise goal-directed attention. Findings showed that only neurotypical adults imitated atypical biological kinematics. Adults with autism did, however, become significantly more accurate at imitating movement time. This confirmed they engaged in the task, and that sensorimotor adaptation was self-regulated. The attentional bias to movement time suggests the attenuation in imitating kinematics might be a compensatory strategy due to deficits in lower-level visuomotor processes associated with self-other mapping, or selective attention modulated the processes that represent biological kinematics.

ClusterViz: A Cytoscape APP for Cluster Analysis of Biological Network.

PubMed

Wang, Jianxin; Zhong, Jiancheng; Chen, Gang; Li, Min; Wu, Fang-xiang; Pan, Yi

2015-01-01

Cluster analysis of biological networks is one of the most important approaches for identifying functional modules and predicting protein functions. Furthermore, visualization of clustering results is crucial to uncover the structure of biological networks. In this paper, ClusterViz, an APP of Cytoscape 3 for cluster analysis and visualization, has been developed. In order to reduce complexity and enable extendibility for ClusterViz, we designed the architecture of ClusterViz based on the framework of Open Services Gateway Initiative. According to the architecture, the implementation of ClusterViz is partitioned into three modules including interface of ClusterViz, clustering algorithms and visualization and export. ClusterViz fascinates the comparison of the results of different algorithms to do further related analysis. Three commonly used clustering algorithms, FAG-EC, EAGLE and MCODE, are included in the current version. Due to adopting the abstract interface of algorithms in module of the clustering algorithms, more clustering algorithms can be included for the future use. To illustrate usability of ClusterViz, we provided three examples with detailed steps from the important scientific articles, which show that our tool has helped several research teams do their research work on the mechanism of the biological networks.

SBROME: a scalable optimization and module matching framework for automated biosystems design.

PubMed

Huynh, Linh; Tsoukalas, Athanasios; Köppe, Matthias; Tagkopoulos, Ilias

2013-05-17

The development of a scalable framework for biodesign automation is a formidable challenge given the expected increase in part availability and the ever-growing complexity of synthetic circuits. To allow for (a) the use of previously constructed and characterized circuits or modules and (b) the implementation of designs that can scale up to hundreds of nodes, we here propose a divide-and-conquer Synthetic Biology Reusable Optimization Methodology (SBROME). An abstract user-defined circuit is first transformed and matched against a module database that incorporates circuits that have previously been experimentally characterized. Then the resulting circuit is decomposed to subcircuits that are populated with the set of parts that best approximate the desired function. Finally, all subcircuits are subsequently characterized and deposited back to the module database for future reuse. We successfully applied SBROME toward two alternative designs of a modular 3-input multiplexer that utilize pre-existing logic gates and characterized biological parts.

Synthetic biology for microbial heavy metal biosensors.

PubMed

Kim, Hyun Ju; Jeong, Haeyoung; Lee, Sang Jun

2018-02-01

Using recombinant DNA technology, various whole-cell biosensors have been developed for detection of environmental pollutants, including heavy metal ions. Whole-cell biosensors have several advantages: easy and inexpensive cultivation, multiple assays, and no requirement of any special techniques for analysis. In the era of synthetic biology, cutting-edge DNA sequencing and gene synthesis technologies have accelerated the development of cell-based biosensors. Here, we summarize current technological advances in whole-cell heavy metal biosensors, including the synthetic biological components (bioparts), sensing and reporter modules, genetic circuits, and chassis cells. We discuss several opportunities for improvement of synthetic cell-based biosensors. First, new functional modules must be discovered in genome databases, and this knowledge must be used to upgrade specific bioparts through molecular engineering. Second, modules must be assembled into functional biosystems in chassis cells. Third, heterogeneity of individual cells in the microbial population must be eliminated. In the perspectives, the development of whole-cell biosensors is also discussed in the aspects of cultivation methods and synthetic cells.

Neuropeptide Substance P and the Immune Response

PubMed Central

Tehrani, Mohsen; Grace, Peter M.; Pothoulakis, Charalabos; Dana, Reza

2016-01-01

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of activity of immune cells. This Review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immuno-biology of substance P and we discuss the clinical implications of its ability to modulate the immune response. PMID:27314883

Space Shuttle Projects

NASA Image and Video Library

1997-01-01

This is a view of the Russian Mir Space Station photographed by a crewmember of the fifth Shuttle/Mir docking mission, STS-81. The image shows: upper center - Progress supply vehicle, Kvant-1 module, and Core module; center left - Priroda module; center right - Spektr module; bottom left - Kvant-2 module; bottom center - Soyuz; and bottom right - Kristall module and Docking module. The Progress was an unmarned, automated version of the Soyuz crew transfer vehicle, designed to resupply the Mir. The Kvant-1 provided research in the physics of galaxies, quasars, and neutron stars, by measuring electromagnetic spectra and x-ray emissions. The Core module served as the heart of the space station and contained the primary living and working areas, life support, and power, as well as the main computer, communications, and control equipment. Priroda's main purpose was Earth remote sensing. The Spektr module provided Earth observation. It also supported research into biotechnology, life sciences, materials science, and space technologies. American astronauts used the Spektr as their living quarters. Kvant-2 was a scientific and airlock module, providing biological research, Earth observations, and EVA (extravehicular activity) capability. The Soyuz typically ferried three crewmembers to and from the Mir. A main purpose of the Kristall module was to develop biological and materials production technologies in the space environment. The Docking module made it possible for the Space Shuttle to dock easily with the Mir. The journey of the 15-year-old Russian Mir Space Station ended March 23, 2001, as the Mir re-entered the Earth's atmosphere and fell into the south Pacific Ocean.

SABRE: a method for assessing the stability of gene modules in complex tissues and subject populations.

PubMed

Shannon, Casey P; Chen, Virginia; Takhar, Mandeep; Hollander, Zsuzsanna; Balshaw, Robert; McManus, Bruce M; Tebbutt, Scott J; Sin, Don D; Ng, Raymond T

2016-11-14

Gene network inference (GNI) algorithms can be used to identify sets of coordinately expressed genes, termed network modules from whole transcriptome gene expression data. The identification of such modules has become a popular approach to systems biology, with important applications in translational research. Although diverse computational and statistical approaches have been devised to identify such modules, their performance behavior is still not fully understood, particularly in complex human tissues. Given human heterogeneity, one important question is how the outputs of these computational methods are sensitive to the input sample set, or stability. A related question is how this sensitivity depends on the size of the sample set. We describe here the SABRE (Similarity Across Bootstrap RE-sampling) procedure for assessing the stability of gene network modules using a re-sampling strategy, introduce a novel criterion for identifying stable modules, and demonstrate the utility of this approach in a clinically-relevant cohort, using two different gene network module discovery algorithms. The stability of modules increased as sample size increased and stable modules were more likely to be replicated in larger sets of samples. Random modules derived from permutated gene expression data were consistently unstable, as assessed by SABRE, and provide a useful baseline value for our proposed stability criterion. Gene module sets identified by different algorithms varied with respect to their stability, as assessed by SABRE. Finally, stable modules were more readily annotated in various curated gene set databases. The SABRE procedure and proposed stability criterion may provide guidance when designing systems biology studies in complex human disease and tissues.

Systematic Biological Filter Design with a Desired I/O Filtering Response Based on Promoter-RBS Libraries.

PubMed

Hsu, Chih-Yuan; Pan, Zhen-Ming; Hu, Rei-Hsing; Chang, Chih-Chun; Cheng, Hsiao-Chun; Lin, Che; Chen, Bor-Sen

2015-01-01

In this study, robust biological filters with an external control to match a desired input/output (I/O) filtering response are engineered based on the well-characterized promoter-RBS libraries and a cascade gene circuit topology. In the field of synthetic biology, the biological filter system serves as a powerful detector or sensor to sense different molecular signals and produces a specific output response only if the concentration of the input molecular signal is higher or lower than a specified threshold. The proposed systematic design method of robust biological filters is summarized into three steps. Firstly, several well-characterized promoter-RBS libraries are established for biological filter design by identifying and collecting the quantitative and qualitative characteristics of their promoter-RBS components via nonlinear parameter estimation method. Then, the topology of synthetic biological filter is decomposed into three cascade gene regulatory modules, and an appropriate promoter-RBS library is selected for each module to achieve the desired I/O specification of a biological filter. Finally, based on the proposed systematic method, a robust externally tunable biological filter is engineered by searching the promoter-RBS component libraries and a control inducer concentration library to achieve the optimal reference match for the specified I/O filtering response.

Lipo-chitin oligosaccharides, plant symbiosis signalling molecules that modulate mammalian angiogenesis in vitro.

PubMed

Djordjevic, Michael A; Bezos, Anna; Susanti; Marmuse, Laurence; Driguez, Hugues; Samain, Eric; Vauzeilles, Boris; Beau, Jean-Marie; Kordbacheh, Farzaneh; Rolfe, Barry G; Schwörer, Ralf; Daines, Alison M; Gresshoff, Peter M; Parish, Christopher R

2014-01-01

Lipochitin oligosaccharides (LCOs) are signaling molecules required by ecologically and agronomically important bacteria and fungi to establish symbioses with diverse land plants. In plants, oligo-chitins and LCOs can differentially interact with different lysin motif (LysM) receptors and affect innate immunity responses or symbiosis-related pathways. In animals, oligo-chitins also induce innate immunity and other physiological responses but LCO recognition has not been demonstrated. Here LCO and LCO-like compounds are shown to be biologically active in mammals in a structure dependent way through the modulation of angiogenesis, a tightly-regulated process involving the induction and growth of new blood vessels from existing vessels. The testing of 24 LCO, LCO-like or oligo-chitin compounds resulted in structure-dependent effects on angiogenesis in vitro leading to promotion, or inhibition or nil effects. Like plants, the mammalian LCO biological activity depended upon the presence and type of terminal substitutions. Un-substituted oligo-chitins of similar chain lengths were unable to modulate angiogenesis indicating that mammalian cells, like plant cells, can distinguish between LCOs and un-substituted oligo-chitins. The cellular mode-of-action of the biologically active LCOs in mammals was determined. The stimulation or inhibition of endothelial cell adhesion to vitronectin or fibronectin correlated with their pro- or anti-angiogenic activity. Importantly, novel and more easily synthesised LCO-like disaccharide molecules were also biologically active and de-acetylated chitobiose was shown to be the primary structural basis of recognition. Given this, simpler chitin disaccharides derivatives based on the structure of biologically active LCOs were synthesised and purified and these showed biological activity in mammalian cells. Since important chronic disease states are linked to either insufficient or excessive angiogenesis, LCO and LCO-like molecules may have the potential to be a new, carbohydrate-based class of therapeutics for modulating angiogenesis.

Modulation of Immune Function by Polyphenols: Possible Contribution of Epigenetic Factors

PubMed Central

Cuevas, Alejandro; Saavedra, Nicolás; Salazar, Luis A.; Abdalla, Dulcineia S. P.

2013-01-01

Several biological activities have been described for polyphenolic compounds, including a modulator effect on the immune system. The effects of these biologically active compounds on the immune system are associated to processes as differentiation and activation of immune cells. Among the mechanisms associated to immune regulation are epigenetic modifications as DNA methylation of regulatory sequences, histone modifications and posttranscriptional repression by microRNAs that influences the gene expression of key players involved in the immune response. Considering that polyphenols are able to regulate the immune function and has been also demonstrated an effect on epigenetic mechanisms, it is possible to hypothesize that there exists a mediator role of epigenetic mechanisms in the modulation of the immune response by polyphenols. PMID:23812304

Aloe vera: Potential candidate in health management via modulation of biological activities

PubMed Central

Rahmani, Arshad H.; Aldebasi, Yousef H.; Srikar, Sauda; Khan, Amjad A.; Aly, Salah M.

2015-01-01

Treatment based on natural products is rapidly increasing worldwide due to the affordability and fewer side effects of such treatment. Various plants and the products derived from them are commonly used in primary health treatment, and they play a pivotal role in the treatment of diseases via modulation of biochemical and molecular pathways. Aloe vera, a succulent species, produces gel and latex, plays a therapeutic role in health management through antioxidant, antitumor, and anti-inflammatory activities, and also offers a suitable alternative approach for the treatment of various types of diseases. In this review, we summarize the possible mechanism of action and the therapeutic implications of Aloe vera in health maintenance based on its modulation of various biological activities. PMID:26392709

GLADIATOR: a global approach for elucidating disease modules.

PubMed

Silberberg, Yael; Kupiec, Martin; Sharan, Roded

2017-05-26

Understanding the genetic basis of disease is an important challenge in biology and medicine. The observation that disease-related proteins often interact with one another has motivated numerous network-based approaches for deciphering disease mechanisms. In particular, protein-protein interaction networks were successfully used to illuminate disease modules, i.e., interacting proteins working in concert to drive a disease. The identification of these modules can further our understanding of disease mechanisms. We devised a global method for the prediction of multiple disease modules simultaneously named GLADIATOR (GLobal Approach for DIsease AssociaTed mOdule Reconstruction). GLADIATOR relies on a gold-standard disease phenotypic similarity to obtain a pan-disease view of the underlying modules. To traverse the search space of potential disease modules, we applied a simulated annealing algorithm aimed at maximizing the correlation between module similarity and the gold-standard phenotypic similarity. Importantly, this optimization is employed over hundreds of diseases simultaneously. GLADIATOR's predicted modules highly agree with current knowledge about disease-related proteins. Furthermore, the modules exhibit high coherence with respect to functional annotations and are highly enriched with known curated pathways, outperforming previous methods. Examination of the predicted proteins shared by similar diseases demonstrates the diverse role of these proteins in mediating related processes across similar diseases. Last, we provide a detailed analysis of the suggested molecular mechanism predicted by GLADIATOR for hyperinsulinism, suggesting novel proteins involved in its pathology. GLADIATOR predicts disease modules by integrating knowledge of disease-related proteins and phenotypes across multiple diseases. The predicted modules are functionally coherent and are more in line with current biological knowledge compared to modules obtained using previous disease-centric methods. The source code for GLADIATOR can be downloaded from http://www.cs.tau.ac.il/~roded/GLADIATOR.zip .

The Role of Reactive Oxygen Species (ROS) in the Biological Activities of Metallic Nanoparticles

PubMed Central

Abdal Dayem, Ahmed; Hossain, Mohammed Kawser; Lee, Soo Bin; Kim, Kyeongseok; Saha, Subbroto Kumar; Yang, Gwang-Mo; Choi, Hye Yeon; Cho, Ssang-Goo

2017-01-01

Nanoparticles (NPs) possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS). The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices. PMID:28075405

Aging effects on DNA methylation modules in human brain and blood tissue

PubMed Central

2012-01-01

Background Several recent studies reported aging effects on DNA methylation levels of individual CpG dinucleotides. But it is not yet known whether aging-related consensus modules, in the form of clusters of correlated CpG markers, can be found that are present in multiple human tissues. Such a module could facilitate the understanding of aging effects on multiple tissues. Results We therefore employed weighted correlation network analysis of 2,442 Illumina DNA methylation arrays from brain and blood tissues, which enabled the identification of an age-related co-methylation module. Module preservation analysis confirmed that this module can also be found in diverse independent data sets. Biological evaluation showed that module membership is associated with Polycomb group target occupancy counts, CpG island status and autosomal chromosome location. Functional enrichment analysis revealed that the aging-related consensus module comprises genes that are involved in nervous system development, neuron differentiation and neurogenesis, and that it contains promoter CpGs of genes known to be down-regulated in early Alzheimer's disease. A comparison with a standard, non-module based meta-analysis revealed that selecting CpGs based on module membership leads to significantly increased gene ontology enrichment, thus demonstrating that studying aging effects via consensus network analysis enhances the biological insights gained. Conclusions Overall, our analysis revealed a robustly defined age-related co-methylation module that is present in multiple human tissues, including blood and brain. We conclude that blood is a promising surrogate for brain tissue when studying the effects of age on DNA methylation profiles. PMID:23034122

Design strategies to address the effect of hydrophobic epitope on stability and in vitro assembly of modular virus‐like particle

PubMed Central

Tekewe, Alemu; Connors, Natalie K.; Middelberg, Anton P. J.

2016-01-01

Abstract Virus‐like particles (VLPs) and capsomere subunits have shown promising potential as safe and effective vaccine candidates. They can serve as platforms for the display of foreign epitopes on their surfaces in a modular architecture. Depending on the physicochemical properties of the antigenic modules, modularization may affect the expression, solubility and stability of capsomeres, and VLP assembly. In this study, three module designs of a rotavirus hydrophobic peptide (RV10) were synthesized using synthetic biology. Among the three synthetic modules, modularization of the murine polyomavirus VP1 with a single copy of RV10 flanked by long linkers and charged residues resulted in the expression of stable modular capsomeres. Further employing the approach of module titration of RV10 modules on each capsomere via Escherichia coli co‐expression of unmodified VP1 and modular VP1‐RV10 successfully translated purified modular capomeres into modular VLPs when assembled in vitro. Our results demonstrate that tailoring the physicochemical properties of modules to enhance modular capsomeres stability is achievable through synthetic biology designs. Combined with module titration strategy to avoid steric hindrance to intercapsomere interactions, this allows bioprocessing of bacterially produced in vitro assembled modular VLPs. PMID:27222486

Design strategies to address the effect of hydrophobic epitope on stability and in vitro assembly of modular virus-like particle.

PubMed

Tekewe, Alemu; Connors, Natalie K; Middelberg, Anton P J; Lua, Linda H L

2016-08-01

Virus-like particles (VLPs) and capsomere subunits have shown promising potential as safe and effective vaccine candidates. They can serve as platforms for the display of foreign epitopes on their surfaces in a modular architecture. Depending on the physicochemical properties of the antigenic modules, modularization may affect the expression, solubility and stability of capsomeres, and VLP assembly. In this study, three module designs of a rotavirus hydrophobic peptide (RV10) were synthesized using synthetic biology. Among the three synthetic modules, modularization of the murine polyomavirus VP1 with a single copy of RV10 flanked by long linkers and charged residues resulted in the expression of stable modular capsomeres. Further employing the approach of module titration of RV10 modules on each capsomere via Escherichia coli co-expression of unmodified VP1 and modular VP1-RV10 successfully translated purified modular capomeres into modular VLPs when assembled in vitro. Our results demonstrate that tailoring the physicochemical properties of modules to enhance modular capsomeres stability is achievable through synthetic biology designs. Combined with module titration strategy to avoid steric hindrance to intercapsomere interactions, this allows bioprocessing of bacterially produced in vitro assembled modular VLPs. © 2016 The Protein Society.

Beyond arousal and valence: the importance of the biological versus social relevance of emotional stimuli.

PubMed

Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

2012-03-01

The present study addressed the hypothesis that emotional stimuli relevant to survival or reproduction (biologically emotional stimuli) automatically affect cognitive processing (e.g., attention, memory), while those relevant to social life (socially emotional stimuli) require elaborative processing to modulate attention and memory. Results of our behavioral studies showed that (1) biologically emotional images hold attention more strongly than do socially emotional images, (2) memory for biologically emotional images was enhanced even with limited cognitive resources, but (3) memory for socially emotional images was enhanced only when people had sufficient cognitive resources at encoding. Neither images' subjective arousal nor their valence modulated these patterns. A subsequent functional magnetic resonance imaging study revealed that biologically emotional images induced stronger activity in the visual cortex and greater functional connectivity between the amygdala and visual cortex than did socially emotional images. These results suggest that the interconnection between the amygdala and visual cortex supports enhanced attention allocation to biological stimuli. In contrast, socially emotional images evoked greater activity in the medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between the amygdala and MPFC than did biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity.

Beyond arousal and valence: The importance of the biological versus social relevance of emotional stimuli

PubMed Central

Sakaki, Michiko; Niki, Kazuhisa; Mather, Mara

2012-01-01

The present study addressed the hypothesis that emotional stimuli relevant to survival or reproduction (biologically emotional stimuli) automatically affect cognitive processing (e.g., attention; memory), while those relevant to social life (socially emotional stimuli) require elaborative processing to modulate attention and memory. Results of our behavioral studies showed that: a) biologically emotional images hold attention more strongly than socially emotional images, b) memory for biologically emotional images was enhanced even with limited cognitive resources, but c) memory for socially emotional images was enhanced only when people had sufficient cognitive resources at encoding. Neither images’ subjective arousal nor their valence modulated these patterns. A subsequent functional magnetic resonance imaging study revealed that biologically emotional images induced stronger activity in visual cortex and greater functional connectivity between amygdala and visual cortex than did socially emotional images. These results suggest that the interconnection between the amygdala and visual cortex supports enhanced attention allocation to biological stimuli. In contrast, socially emotional images evoked greater activity in medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between amygdala and MPFC than biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity. PMID:21964552

3D printing of tissue-simulating phantoms as a traceable standard for biomedical optical measurement

NASA Astrophysics Data System (ADS)

Dong, Erbao; Wang, Minjie; Shen, Shuwei; Han, Yilin; Wu, Qiang; Xu, Ronald

2016-01-01

Optical phantoms are commonly used to validate and calibrate biomedical optical devices in order to ensure accurate measurement of optical properties in biological tissue. However, commonly used optical phantoms are based on homogenous materials that reflect neither optical properties nor multi-layer heterogeneities of biological tissue. Using these phantoms for optical calibration may result in significant bias in biological measurement. We propose to characterize and fabricate tissue simulating phantoms that simulate not only the multi-layer heterogeneities but also optical properties of biological tissue. The tissue characterization module detects tissue structural and functional properties in vivo. The phantom printing module generates 3D tissue structures at different scales by layer-by-layer deposition of phantom materials with different optical properties. The ultimate goal is to fabricate multi-layer tissue simulating phantoms as a traceable standard for optimal calibration of biomedical optical spectral devices.

An autonomous molecular computer for logical control of gene expression.

PubMed

Benenson, Yaakov; Gil, Binyamin; Ben-Dor, Uri; Adar, Rivka; Shapiro, Ehud

2004-05-27

Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems. Recently, simple molecular-scale autonomous programmable computers were demonstrated allowing both input and output information to be in molecular form. Such computers, using biological molecules as input data and biologically active molecules as outputs, could produce a system for 'logical' control of biological processes. Here we describe an autonomous biomolecular computer that, at least in vitro, logically analyses the levels of messenger RNA species, and in response produces a molecule capable of affecting levels of gene expression. The computer operates at a concentration of close to a trillion computers per microlitre and consists of three programmable modules: a computation module, that is, a stochastic molecular automaton; an input module, by which specific mRNA levels or point mutations regulate software molecule concentrations, and hence automaton transition probabilities; and an output module, capable of controlled release of a short single-stranded DNA molecule. This approach might be applied in vivo to biochemical sensing, genetic engineering and even medical diagnosis and treatment. As a proof of principle we programmed the computer to identify and analyse mRNA of disease-related genes associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modelled after an anticancer drug.

Manipulating and Monitoring On-Surface Biological Reactions by Light-Triggered Local pH Alterations.

PubMed

Peretz-Soroka, Hagit; Pevzner, Alexander; Davidi, Guy; Naddaka, Vladimir; Kwiat, Moria; Huppert, Dan; Patolsky, Fernando

2015-07-08

Significant research efforts have been dedicated to the integration of biological species with electronic elements to yield smart bioelectronic devices. The integration of DNA, proteins, and whole living cells and tissues with electronic devices has been developed into numerous intriguing applications. In particular, the quantitative detection of biological species and monitoring of biological processes are both critical to numerous areas of medical and life sciences. Nevertheless, most current approaches merely focus on the "monitoring" of chemical processes taking place on the sensing surfaces, and little efforts have been invested in the conception of sensitive devices that can simultaneously "control" and "monitor" chemical and biological reactions by the application of on-surface reversible stimuli. Here, we demonstrate the light-controlled fine modulation of surface pH by the use of photoactive molecularly modified nanomaterials. Through the use of nanowire-based FET devices, we showed the capability of modulating the on-surface pH, by intensity-controlled light stimulus. This allowed us simultaneously and locally to control and monitor pH-sensitive biological reactions on the nanodevices surfaces, such as the local activation and inhibition of proteolytic enzymatic processes, as well as dissociation of antigen-antibody binding interactions. The demonstrated capability of locally modulating the on-surface effective pH, by a light stimuli, may be further applied in the local control of on-surface DNA hybridization/dehybridization processes, activation or inhibition of living cells processes, local switching of cellular function, local photoactivation of neuronal networks with single cell resolution and so forth.

Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-15-1-0512 TITLE: Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer PRINCIPAL INVESTIGATOR: Andrew...SUBTITLE 5a. CONTRACT NUMBER Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0512 5c. PROGRAM...blocked by the addition of Pim inhibitors. These results suggest that the Pim protein kinase can regulate stromal cell biology to modulate epithelial

Regulating Cancer Associated Fibroblast Biology in Prostate Cancer

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0512 TITLE: Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer PRINCIPAL INVESTIGATOR: Andrew...CONTRACT NUMBER Regulating Cancer-Associated Fibroblast Biology in Prostate Cancer 5b. GRANT NUMBER W81XWH-15-1-0512 5c. PROGRAM ELEMENT NUMBER 6... biology to modulate epithelial growth and that inhibitors of this protein kinase have the potential to block this process and thus inhibit tumor growth

Alcohol Pharmacology Education Partnership: Using Chemistry and Biology Concepts to Educate High School Students about Alcohol

ERIC Educational Resources Information Center

Godin, Elizabeth A.; Kwiek, Nicole; Sikes, Suzanne S.; Halpin, Myra J.; Weinbaum, Carolyn A.; Burgette, Lane F.; Reiter, Jerome P.; Schwartz-Bloom, Rochelle D.

2014-01-01

We developed the Alcohol Pharmacology Education Partnership (APEP), a set of modules designed to integrate a topic of interest (alcohol) with concepts in chemistry and biology for high school students. Chemistry and biology teachers (n = 156) were recruited nationally to field-test APEP in a controlled study. Teachers obtained professional…

Piquing Student Interest with Pharmacology: An Interdisciplinary Program Helps High School Students Learn Biology and Chemistry Principles

ERIC Educational Resources Information Center

Halpin, Myra J.; Hoeffler, Leanne; Schwartz-Bloom, Rochelle D.

2005-01-01

To help students learn science concepts, Pharmacology Education Partnership (PEP)--a science education program that incorporates relevant topics related to drugs and drug abuse into standard biology and chemistry curricula was developed. The interdisciplinary PEP curriculum provides six modules to teach biology and chemistry principles within the…

Integration of Biological Applications into the Core Undergraduate Curriculum: A Practical Strategy

ERIC Educational Resources Information Center

Komives, Claire; Prince, Michael; Fernandez, Erik; Balcarcel, Robert

2011-01-01

A web database of solved problems has been created to enable faculty to incorporate biological applications into core courses. Over 20% of US ChE departments utilized problems from the website, and 19 faculty attended a workshop to facilitate teaching the modules. Assessment of student learning showed some gains related to biological outcomes, as…

"Cancer Cell Biology:" A Student-Centered Instructional Module Exploring the Use of Multimedia to Enrich Interactive, Constructivist Learning of Science

ERIC Educational Resources Information Center

Bockholt, Susanne M.; West, J. Paige; Bollenbacher, Walter E.

2003-01-01

Multimedia has the potential of providing bioscience education novel learning environments and pedagogy applications to foster student interest, involve students in the research process, advance critical thinking/problem-solving skills, and develop conceptual understanding of biological topics. "Cancer Cell Biology," an interactive, multimedia,…

Project COLD.

ERIC Educational Resources Information Center

Kazanjian, Wendy C.

1982-01-01

Describes Project COLD (Climate, Ocean, Land, Discovery) a scientific study of the Polar Regions, a collection of 35 modules used within the framework of existing subjects: oceanography, biology, geology, meterology, geography, social science. Includes a partial list of topics and one activity (geodesic dome) from a module. (Author/SK)

GOMA: functional enrichment analysis tool based on GO modules

PubMed Central

Huang, Qiang; Wu, Ling-Yun; Wang, Yong; Zhang, Xiang-Sun

2013-01-01

Analyzing the function of gene sets is a critical step in interpreting the results of high-throughput experiments in systems biology. A variety of enrichment analysis tools have been developed in recent years, but most output a long list of significantly enriched terms that are often redundant, making it difficult to extract the most meaningful functions. In this paper, we present GOMA, a novel enrichment analysis method based on the new concept of enriched functional Gene Ontology (GO) modules. With this method, we systematically revealed functional GO modules, i.e., groups of functionally similar GO terms, via an optimization model and then ranked them by enrichment scores. Our new method simplifies enrichment analysis results by reducing redundancy, thereby preventing inconsistent enrichment results among functionally similar terms and providing more biologically meaningful results. PMID:23237213

Stochastic blockmodeling of the modules and core of the Caenorhabditis elegans connectome.

PubMed

Pavlovic, Dragana M; Vértes, Petra E; Bullmore, Edward T; Schafer, William R; Nichols, Thomas E

2014-01-01

Recently, there has been much interest in the community structure or mesoscale organization of complex networks. This structure is characterised either as a set of sparsely inter-connected modules or as a highly connected core with a sparsely connected periphery. However, it is often difficult to disambiguate these two types of mesoscale structure or, indeed, to summarise the full network in terms of the relationships between its mesoscale constituents. Here, we estimate a community structure with a stochastic blockmodel approach, the Erdős-Rényi Mixture Model, and compare it to the much more widely used deterministic methods, such as the Louvain and Spectral algorithms. We used the Caenorhabditis elegans (C. elegans) nervous system (connectome) as a model system in which biological knowledge about each node or neuron can be used to validate the functional relevance of the communities obtained. The deterministic algorithms derived communities with 4-5 modules, defined by sparse inter-connectivity between all modules. In contrast, the stochastic Erdős-Rényi Mixture Model estimated a community with 9 blocks or groups which comprised a similar set of modules but also included a clearly defined core, made of 2 small groups. We show that the "core-in-modules" decomposition of the worm brain network, estimated by the Erdős-Rényi Mixture Model, is more compatible with prior biological knowledge about the C. elegans nervous system than the purely modular decomposition defined deterministically. We also show that the blockmodel can be used both to generate stochastic realisations (simulations) of the biological connectome, and to compress network into a small number of super-nodes and their connectivity. We expect that the Erdős-Rényi Mixture Model may be useful for investigating the complex community structures in other (nervous) systems.

A New Role Change Approach in Pre-service Teacher Education for Developing Pedagogical Content Knowledge in the Context of a Student Outreach Lab

NASA Astrophysics Data System (ADS)

Scharfenberg, Franz-Josef; Bogner, Franz X.

2016-10-01

How pre-service teachers (PST) develop pedagogical content knowledge (PCK) during science teacher education is an open research question. Our teacher education module, theoretically based on PCK, specifically combines biology PSTs' education with high school students' biology education and includes an innovative role change approach. Altogether, 41 PSTs each participated in three subsequent module days with students ( N = 823) from 50 classes. The module's content dealt with the syllabus topic Genetic Fingerprinting. During participation, the PSTs changed their role by assuming a student's role on the first day, a tutor's role on the second day, and a teacher's role on the third day. By quasi-experimentally administering pre- and delayed posttests, we qualitatively monitored, then content-analytically categorized, and finally quantitatively analyzed three specific PCK components. In contrast to a control group (which did not participate in the module), our treatment preferentially changed the PSTs' orientations toward teaching biology to a more student-centered orientation (both intra- and inter-group differences with medium effect sizes). Additionally, the PSTs who participated in the three modules days differed before and after module participation in how they addressed potential student learning difficulties and identified potential instructional strategies for avoiding these difficulties. The changes in these PCK components point to a step-by-step development of the PSTs' PCK. In this process, our participating PSTs assessed the importance of their three roles on the 3 days quite differently; most notably, we found one relationship between the teacher role and the PSTs' student-centeredness. We specifically discuss the potential and importance of our role change approach within science teacher education.

A Systematic Protocol for the Characterization of Hsp90 Modulators

PubMed Central

Matts, Robert L.; Brandt, Gary E. L.; Lu, Yuanming; Dixit, Anshuman; Mollapour, Mehdi; Wang, Suiquan; Donnelly, Alison C.; Neckers, Leonard; Verkhivker, Gennady; Blagg, Brian S. J.

2015-01-01

Several Hsp90 modulators have been identified including the N-terminal ligand geldanamycin (GDA), the C-terminal ligand novobiocin (NB), and the co-chaperone disruptor celastrol. Other Hsp90 modulators elicit a mechanism of action that remains unknown. For example, the natural product gedunin and the synthetic anti-spermatogenic agent H2-gamendazole, recently identified Hsp90 modulators, manifest biological activity through undefined mechanisms. Herein, we report a series of biochemical techniques used to classify such modulators into identifiable categories. Such studies provided evidence that gedunin and H2-gamendazole both modulate Hsp90 via a mechanism similar to celastrol, and unlike NB or GDA. PMID:21129982

How chemistry supports cell biology: the chemical toolbox at your service.

PubMed

Wijdeven, Ruud H; Neefjes, Jacques; Ovaa, Huib

2014-12-01

Chemical biology is a young and rapidly developing scientific field. In this field, chemistry is inspired by biology to create various tools to monitor and modulate biochemical and cell biological processes. Chemical contributions such as small-molecule inhibitors and activity-based probes (ABPs) can provide new and unique insights into previously unexplored cellular processes. This review provides an overview of recent breakthroughs in chemical biology that are likely to have a significant impact on cell biology. We also discuss the application of several chemical tools in cell biology research. Copyright © 2014 Elsevier Ltd. All rights reserved.

New extension software modules to enhance searching and display of transcriptome data in Tripal databases

PubMed Central

Chen, Ming; Henry, Nathan; Almsaeed, Abdullah; Zhou, Xiao; Wegrzyn, Jill; Ficklin, Stephen

2017-01-01

Abstract Tripal is an open source software package for developing biological databases with a focus on genetic and genomic data. It consists of a set of core modules that deliver essential functions for loading and displaying data records and associated attributes including organisms, sequence features and genetic markers. Beyond the core modules, community members are encouraged to contribute extension modules to build on the Tripal core and to customize Tripal for individual community needs. To expand the utility of the Tripal software system, particularly for RNASeq data, we developed two new extension modules. Tripal Elasticsearch enables fast, scalable searching of the entire content of a Tripal site as well as the construction of customized advanced searches of specific data types. We demonstrate the use of this module for searching assembled transcripts by functional annotation. A second module, Tripal Analysis Expression, houses and displays records from gene expression assays such as RNA sequencing. This includes biological source materials (biomaterials), gene expression values and protocols used to generate the data. In the case of an RNASeq experiment, this would reflect the individual organisms and tissues used to produce sequencing libraries, the normalized gene expression values derived from the RNASeq data analysis and a description of the software or code used to generate the expression values. The module will load data from common flat file formats including standard NCBI Biosample XML. Data loading, display options and other configurations can be controlled by authorized users in the Drupal administrative backend. Both modules are open source, include usage documentation, and can be found in the Tripal organization’s GitHub repository. Database URL: Tripal Elasticsearch module: https://github.com/tripal/tripal_elasticsearch Tripal Analysis Expression module: https://github.com/tripal/tripal_analysis_expression PMID:29220446

Evaluating the effectiveness of a practical inquiry-based learning bioinformatics module on undergraduate student engagement and applied skills.

PubMed

Brown, James A L

2016-05-06

A pedagogic intervention, in the form of an inquiry-based peer-assisted learning project (as a practical student-led bioinformatics module), was assessed for its ability to increase students' engagement, practical bioinformatic skills and process-specific knowledge. Elements assessed were process-specific knowledge following module completion, qualitative student-based module evaluation and the novelty, scientific validity and quality of written student reports. Bioinformatics is often the starting point for laboratory-based research projects, therefore high importance was placed on allowing students to individually develop and apply processes and methods of scientific research. Students led a bioinformatic inquiry-based project (within a framework of inquiry), discovering, justifying and exploring individually discovered research targets. Detailed assessable reports were produced, displaying data generated and the resources used. Mimicking research settings, undergraduates were divided into small collaborative groups, with distinctive central themes. The module was evaluated by assessing the quality and originality of the students' targets through reports, reflecting students' use and understanding of concepts and tools required to generate their data. Furthermore, evaluation of the bioinformatic module was assessed semi-quantitatively using pre- and post-module quizzes (a non-assessable activity, not contributing to their grade), which incorporated process- and content-specific questions (indicative of their use of the online tools). Qualitative assessment of the teaching intervention was performed using post-module surveys, exploring student satisfaction and other module specific elements. Overall, a positive experience was found, as was a post module increase in correct process-specific answers. In conclusion, an inquiry-based peer-assisted learning module increased students' engagement, practical bioinformatic skills and process-specific knowledge. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:304-313 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

PyPathway: Python Package for Biological Network Analysis and Visualization.

PubMed

Xu, Yang; Luo, Xiao-Chun

2018-05-01

Life science studies represent one of the biggest generators of large data sets, mainly because of rapid sequencing technological advances. Biological networks including interactive networks and human curated pathways are essential to understand these high-throughput data sets. Biological network analysis offers a method to explore systematically not only the molecular complexity of a particular disease but also the molecular relationships among apparently distinct phenotypes. Currently, several packages for Python community have been developed, such as BioPython and Goatools. However, tools to perform comprehensive network analysis and visualization are still needed. Here, we have developed PyPathway, an extensible free and open source Python package for functional enrichment analysis, network modeling, and network visualization. The network process module supports various interaction network and pathway databases such as Reactome, WikiPathway, STRING, and BioGRID. The network analysis module implements overrepresentation analysis, gene set enrichment analysis, network-based enrichment, and de novo network modeling. Finally, the visualization and data publishing modules enable users to share their analysis by using an easy web application. For package availability, see the first Reference.

Functional modules of sigma factor regulons guarantee adaptability and evolvability

PubMed Central

Binder, Sebastian C.; Eckweiler, Denitsa; Schulz, Sebastian; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Häussler, Susanne; Meyer-Hermann, Michael

2016-01-01

The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability. PMID:26915971

Sugar-Coated PPE's, Novel Nanomaterial's and Sensing Modules for Disease and Bioterrorism Related Threats

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

Bunz, Uwe

2003-11-21

The detection and sensing of biological warfare agents (ricin, anthrax toxin), of disease agents (cholera, botulinum, and tetnus toxins, influenza virus, etc.) and of biologically active species important for national security and disease control.

Exploring protein structure and dynamics through a project-oriented biochemistry laboratory module.

PubMed

Lipchock, James M; Ginther, Patrick S; Douglas, Bonnie B; Bird, Kelly E; Patrick Loria, J

2017-09-01

Here, we present a 10-week project-oriented laboratory module designed to provide a course-based undergraduate research experience in biochemistry that emphasizes the importance of biomolecular structure and dynamics in enzyme function. This module explores the impact of mutagenesis on an important active site loop for a biomedically-relevant human enzyme, protein tyrosine phosphatase 1B (PTP1B). Over the course of the semester students guide their own mutant of PTP1B from conception to characterization in a cost-effective manner and gain exposure to fundamental techniques in biochemistry, including site-directed DNA mutagenesis, bacterial recombinant protein expression, affinity column purification, protein quantitation, SDS-PAGE, and enzyme kinetics. This project-based approach allows an instructor to simulate a research setting and prepare students for productive research beyond the classroom. Potential modifications to expand or contract this module are also provided. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):403-410, 2017. © 2017 The International Union of Biochemistry and Molecular Biology.

FOST 2 Upgrade with Hollow-Fiber CTA FO Module and Generation of Osmotic Agent for Microorganism Growth Studies

NASA Technical Reports Server (NTRS)

Parodi, Jurek; Mangado, Jaione Romero; Stefanson, Ofir; Flynn, Michael; Shaw, Hali; Beeler, David

2016-01-01

FOST 2 is an integrated membrane system that incorporates a forward osmosis subsystem and a reverse osmosis subsystem working in series. It has been designed as a post treatment system to process the effluent from the Membrane Aerated Biological Reactor developed at NASA Johnson Space Center and Texas Tech University. Its function is to remove dissolved solids residual such as ammonia and suspended solids, as well as to provide a physical barrier to microbial and viral contamination. A tubular CTA membrane module from HTI and a flat-sheet lipid-base membrane module from Porifera were integrated and tested on FOST 2 in the past, using both a bioreactor's effluent and greywater as the feed solution. This paper documents the performance of FOST 2 after its upgrade with a hollow-fiber CTA membrane module from Toyobo, treating real black-water to generate the osmotic agent solution necessary to conduct growth studies of genetically engineered microorganism for the Synthetic Biological Membrane project.

Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65

PubMed Central

Huang, Xi-Ping; Karpiak, Joel; Kroeze, Wesley K.; Zhu, Hu; Chen, Xin; Moy, Sheryl S.; Saddoris, Kara A.; Nikolova, Viktoriya; Farrell, Martilias S.; Wang, Sheng; Mangano, Thomas J.; Deshpande, Deepak A.; Jiang, Alice; Penn, Raymond B.; Jin, Jian; Koller, Beverly H.; Kenakin, Terry; Shoichet, Brian K.; Roth, Bryan L.

2016-01-01

At least 120 non-olfactory G protein-coupled receptors in the human genome are ”orphans” for which endogenous ligands are unknown, and many have no selective ligands, hindering elucidation of their biological functions and clinical relevance. Among these is GPR68, a proton receptor that lacks small molecule modulators for probing its biology. Yeast-based screens against GPR68 identified the benzodiazepine drug lorazepam as a non-selective GPR68 positive allosteric modulator. Over 3000 GPR68 homology models were refined to recognize lorazepam in a putative allosteric site. Docking 3.1 million molecules predicted new GPR68 modulators many of which were confirmed in functional assays. One potent GPR68 modulator—ogerin– suppressed recall in fear conditioning in wild-type, but not in GPR68 knockout mice. The same approach led to the discovery of allosteric agonists and negative allosteric modulators for GPR65. Combining physical and structure-based screening may be broadly useful for ligand discovery for understudied and orphan GPCRs. PMID:26550826

Designed multiple ligands in metabolic disease research: from concept to platform.

PubMed

Gattrell, W; Johnstone, C; Patel, S; Smith, C Sambrook; Scheel, A; Schindler, M

2013-08-01

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and drug monotherapy typically results in unsatisfactory treatment outcomes for patients. Even when used in combination, existing therapies lack efficacy in the long term. Designed multiple ligands (DMLs) are compounds developed to modulate multiple targets relevant to a disease. DMLs offer the potential to yield greater efficacy over monotherapies, either by modulating different biological pathways, or by boosting a single one. However, examples of DMLs progressing into clinical trials, or onto the market are rare; DML drug discovery is challenging, and perceived by some to be almost impossible. Nevertheless, with the judicious selection of biological targets, both from a biological and chemical perspective, it is possible to develop drug-like DMLs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mangiferin Modulation of Metabolism and Metabolic Syndrome

PubMed Central

Fomenko, Ekaterina Vladimirovna; Chi, Yuling

2016-01-01

The recent emergence of a worldwide epidemic of metabolic disorders, such as obesity and diabetes, demands effective strategy to develop nutraceuticals or pharmaceuticals to halt this trend. Natural products have long been and continue to be an attractive source of nutritional and pharmacological therapeutics. One such natural product is mangiferin (MGF), the predominant constituent of extracts of the mango plant Mangifera indica L. Reports on biological and pharmacological effects of MGF increased exponentially in recent years. MGF has documented antioxidant and anti-inflammatory effects. Recent studies indicate that it modulates multiple biological processes involved in metabolism of carbohydrates and lipids. MGF has been shown to improve metabolic abnormalities and disorders in animal models and humans. This review focuses on the recently reported biological and pharmacological effects of MGF on metabolism and metabolic disorders. PMID:27534809

Integrated Module and Gene-Specific Regulatory Inference Implicates Upstream Signaling Networks

PubMed Central

Roy, Sushmita; Lagree, Stephen; Hou, Zhonggang; Thomson, James A.; Stewart, Ron; Gasch, Audrey P.

2013-01-01

Regulatory networks that control gene expression are important in diverse biological contexts including stress response and development. Each gene's regulatory program is determined by module-level regulation (e.g. co-regulation via the same signaling system), as well as gene-specific determinants that can fine-tune expression. We present a novel approach, Modular regulatory network learning with per gene information (MERLIN), that infers regulatory programs for individual genes while probabilistically constraining these programs to reveal module-level organization of regulatory networks. Using edge-, regulator- and module-based comparisons of simulated networks of known ground truth, we find MERLIN reconstructs regulatory programs of individual genes as well or better than existing approaches of network reconstruction, while additionally identifying modular organization of the regulatory networks. We use MERLIN to dissect global transcriptional behavior in two biological contexts: yeast stress response and human embryonic stem cell differentiation. Regulatory modules inferred by MERLIN capture co-regulatory relationships between signaling proteins and downstream transcription factors thereby revealing the upstream signaling systems controlling transcriptional responses. The inferred networks are enriched for regulators with genetic or physical interactions, supporting the inference, and identify modules of functionally related genes bound by the same transcriptional regulators. Our method combines the strengths of per-gene and per-module methods to reveal new insights into transcriptional regulation in stress and development. PMID:24146602

Using a Module-Based Laboratory to Incorporate Inquiry into a Large Cell Biology Course

ERIC Educational Resources Information Center

Howard, David R.; Miskowski, Jennifer A.

2005-01-01

Because cell biology has rapidly increased in breadth and depth, instructors are challenged not only to provide undergraduate science students with a strong, up-to-date foundation of knowledge, but also to engage them in the scientific process. To these ends, revision of the Cell Biology Lab course at the University of Wisconsin-La Crosse was…

Assessment of ultrasound modulation of near infrared light on the quantification of scattering coefficient.

PubMed

Singh, M Suheshkumar; Yalavarthy, Phaneendra K; Vasu, R M; Rajan, K

2010-07-01

To assess the effect of ultrasound modulation of near infrared (NIR) light on the quantification of scattering coefficient in tissue-mimicking biological phantoms. A unique method to estimate the phase of the modulated NIR light making use of only time averaged intensity measurements using a charge coupled device camera is used in this investigation. These experimental measurements from tissue-mimicking biological phantoms are used to estimate the differential pathlength, in turn leading to estimation of optical scattering coefficient. A Monte-Carlo model based numerical estimation of phase in lieu of ultrasound modulation is performed to verify the experimental results. The results indicate that the ultrasound modulation of NIR light enhances the effective scattering coefficient. The observed effective scattering coefficient enhancement in tissue-mimicking viscoelastic phantoms increases with increasing ultrasound drive voltage. The same trend is noticed as the ultrasound modulation frequency approaches the natural vibration frequency of the phantom material. The contrast enhancement is less for the stiffer (larger storage modulus) tissue, mimicking tumor necrotic core, compared to the normal tissue. The ultrasound modulation of the insonified region leads to an increase in the effective number of scattering events experienced by NIR light, increasing the measured phase, causing the enhancement in the effective scattering coefficient. The ultrasound modulation of NIR light could provide better estimation of scattering coefficient. The observed local enhancement of the effective scattering coefficient, in the ultrasound focal region, is validated using both experimental measurements and Monte-Carlo simulations.

Constructive biology and approaches to temporal grounding in postreactive robotics

NASA Astrophysics Data System (ADS)

Nehaniv, Chrystopher L.; Dautenhahn, Kerstin; Loomes, Martin J.

1999-08-01

Constructive Biology means understanding biological mechanisms through building systems that exhibit life-like properties. Applications include learning engineering tricks from biological system, as well as the validation in biological modeling. In particular, biological system in the course of development and experience become temporally grounded. Researchers attempting to transcend mere reactivity have been inspired by the drives, motivations, homeostasis, hormonal control, and emotions of animals. In order to contextualize and modulate behavior, these ideas have been introduced into robotics and synthetic agents, while further flexibility is achieved by introducing learning. Broadening scope of the temporal horizon further requires post-reactive techniques that address not only the action in the now, although such action may perhaps be modulated by drives and affect. Support is needed for expressing and benefitting from pats experiences, predictions of the future, and form interaction histories of the self with the world and with other agents. Mathematical methods provide a new way to support such grounding in the construction of post-reactive systems. Moreover, the communication of such mathematical encoded histories of experience between situated agents opens a route to narrative intelligence, analogous to communication or story telling in societies.

Emerging Importance of Phytochemicals in Regulation of Stem Cells Fate via Signaling Pathways.

PubMed

Dadashpour, Mehdi; Pilehvar-Soltanahmadi, Younes; Zarghami, Nosratollah; Firouzi-Amandi, Akram; Pourhassan-Moghaddam, Mohammad; Nouri, Mohammad

2017-11-01

To reach ideal therapeutic potential of stem cells for regenerative medicine purposes, it is essential to retain their self-renewal and differentiation capacities. Currently, biological factors are extensively used for stemness maintaining and differentiation induction of stem cells. However, low stability, high cost, complicated production process, and risks associated with viral/endotoxin infection hamper the widespread use of biological factors in the stem cell biology. Moreover, regarding the modulation of several signaling cascades, which lead to a distinct fate, phytochemicals are preferable in the stem cells biology because of their efficiency. Considering the issues related to the application of biological factors and potential advantages of phytochemicals in stem cell engineering, there is a considerable increasing trend in studies associated with the application of novel alternative molecules in the stem cell biology. In support of this statement, we aimed to highlight the various effects of phytochemicals on signaling cascades involved in commitment of stem cells. Hence, in this review, the current trends in the phytochemicals-based modulation of stem cell fate have been addressed. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Discovering perturbation of modular structure in HIV progression by integrating multiple data sources through non-negative matrix factorization.

PubMed

Ray, Sumanta; Maulik, Ujjwal

2016-12-20

Detecting perturbation in modular structure during HIV-1 disease progression is an important step to understand stage specific infection pattern of HIV-1 virus in human cell. In this article, we proposed a novel methodology on integration of multiple biological information to identify such disruption in human gene module during different stages of HIV-1 infection. We integrate three different biological information: gene expression information, protein-protein interaction information and gene ontology information in single gene meta-module, through non negative matrix factorization (NMF). As the identified metamodules inherit those information so, detecting perturbation of these, reflects the changes in expression pattern, in PPI structure and in functional similarity of genes during the infection progression. To integrate modules of different data sources into strong meta-modules, NMF based clustering is utilized here. Perturbation in meta-modular structure is identified by investigating the topological and intramodular properties and putting rank to those meta-modules using a rank aggregation algorithm. We have also analyzed the preservation structure of significant GO terms in which the human proteins of the meta-modules participate. Moreover, we have performed an analysis to show the change of coregulation pattern of identified transcription factors (TFs) over the HIV progression stages.

The OBIS Trail Module. Trial Version.

ERIC Educational Resources Information Center

Fairwell, Kay, Ed.; And Others

Designed to allow youngsters aged 10 to 15 to experience the challenges and problems environmental investigators might face making an environmental impact study, the trial version of the Outdoor Biology Instructional Strategies (OBIS) Trail Module focuses on aspects of construction-related environment problems. Four activities are included in the…

A shortcut to wide-ranging biological actions of dietary polyphenols: modulation of the nitrate-nitrite-nitric oxide pathway in the gut.

PubMed

Rocha, Bárbara S; Nunes, Carla; Pereira, Cassilda; Barbosa, Rui M; Laranjinha, João

2014-08-01

Dietary polyphenols are complex, natural compounds with recognized health benefits. Initially attractive to the biomedical area due to their in vitro antioxidant properties, the biological implications of polyphenols are now known to be far from their acute ability to scavenge free radicals but rather to modulate redox signaling pathways. Actually, it is now recognized that dietary polyphenols are extensively metabolized in vivo and that the chemical, biophysical and biological properties of their metabolites are, in most cases, quite different from the ones of the parent molecules. Hence, the study of the metabolic, absorptive and signaling pathways of both phenolics and derivatives has become a major issue. In this paper we propose a short-cut for the systemic effects of polyphenols in connection with nitric oxide (˙NO) biology. This free radical is a ubiquitous signaling molecule with pivotal functions in vivo. It is produced through an enzymatic pathway and also through the reduction of dietary nitrate and nitrite in the human stomach. At acidic gastric pH, dietary polyphenols, in the form they are conveyed in foods and at high concentration, not only promote nitrite reduction to ˙NO but also embark in a complex network of chemical reactions to produce higher nitrogen oxides with signaling functions, namely by inducing post-translational modifications. Modified endogenous molecules, such as nitrated proteins and lipids, acquire important physiological functions. Thus, local and systemic effects of ˙NO such as modulation of vascular tone, mucus production in the gut and protection against ischemia-reperfusion injury are, in this sense, triggered by dietary polyphenols. Evidence to support the signaling and biological effects of polyphenols by modulation of the nitrate-nitrite-NO pathway will be herein provided and discussed. General actions of polyphenols encompassing absorption and metabolism in the intestine/liver are short-cut via the production of diffusible species in the stomach that have not only a local but also a general impact.

Ion channel blockers for the treatment of neuropathic pain.

PubMed

Colombo, Elena; Francisconi, Simona; Faravelli, Laura; Izzo, Emanuela; Pevarello, Paolo

2010-05-01

Neuropathic pain, a severe chronic pain condition characterized by a complex pathophysiology, is a largely unmet medical need. Ion channels, which underlie cell excitability, are heavily implicated in the biological mechanisms that generate and sustain neuropathic pain. This review highlights the biological evidence supporting the involvement of voltage-, proton- and ligand-gated ion channels in the neuropathic pain setting. Ion channel modulators at different research or development stages are reviewed and referenced. Ion channel modulation is one of the main avenues to achieve novel, improved neuropathic pain treatments. Voltage-gated sodium and calcium channel and glutamate receptor modulators are likely to produce new, improved agents in the future. Rationally targeting subtypes of known ion channels, tackling recently discovered ion channel targets or combining drugs with different mechanism of action will be primary sources of new drugs in the longer term.

CARS module for multimodal microscopy

NASA Astrophysics Data System (ADS)

Zadoyan, Ruben; Baldacchini, Tommaso; Carter, John; Kuo, Chun-Hung; Ocepek, David

2011-03-01

We describe a stand alone CARS module allowing upgrade of a two-photon microscope with CARS modality. The Stokes beam is generated in a commercially available photonic crystal fiber (PCF) using fraction of the power of femtosecond excitation laser. The output of the fiber is optimized for broadband CARS at Stokes shifts in 2900cm-1 region. The spectral resolution in CARS signal is 50 cm-1. It is achieved by introducing a bandpass filter in the pump beam. The timing between the pump and Stokes pulses is preset inside the module and can be varied. We demonstrate utility of the device on examples of second harmonic, two-photon fluorescence and CARS images of several biological and non-biological samples. We also present results of studies where we used CARS modality to monitor in real time the process of fabrication of microstructures by two-photon polymerization.

How to assign a (3 + 1)-dimensional superspace group to an incommensurately modulated biological macromolecular crystal

PubMed Central

2017-01-01

Periodic crystal diffraction is described using a three-dimensional (3D) unit cell and 3D space-group symmetry. Incommensurately modulated crystals are a subset of aperiodic crystals that need four to six dimensions to describe the observed diffraction pattern, and they have characteristic satellite reflections that are offset from the main reflections. These satellites have a non-integral relationship to the primary lattice and require q vectors for processing. Incommensurately modulated biological macromolecular crystals have been frequently observed but so far have not been solved. The authors of this article have been spearheading an initiative to determine this type of crystal structure. The first step toward structure solution is to collect the diffraction data making sure that the satellite reflections are well separated from the main reflections. Once collected they can be integrated and then scaled with appropriate software. Then the assignment of the superspace group is needed. The most common form of modulation is in only one extra direction and can be described with a (3 + 1)D superspace group. The (3 + 1)D superspace groups for chemical crystallographers are fully described in Volume C of International Tables for Crystallography. This text includes all types of crystallographic symmetry elements found in small-molecule crystals and can be difficult for structural biologists to understand and apply to their crystals. This article provides an explanation for structural biologists that includes only the subset of biological symmetry elements and demonstrates the application to a real-life example of an incommensurately modulated protein crystal. PMID:28808437

Identification of functional modules using network topology and high-throughput data.

PubMed

Ulitsky, Igor; Shamir, Ron

2007-01-26

With the advent of systems biology, biological knowledge is often represented today by networks. These include regulatory and metabolic networks, protein-protein interaction networks, and many others. At the same time, high-throughput genomics and proteomics techniques generate very large data sets, which require sophisticated computational analysis. Usually, separate and different analysis methodologies are applied to each of the two data types. An integrated investigation of network and high-throughput information together can improve the quality of the analysis by accounting simultaneously for topological network properties alongside intrinsic features of the high-throughput data. We describe a novel algorithmic framework for this challenge. We first transform the high-throughput data into similarity values, (e.g., by computing pairwise similarity of gene expression patterns from microarray data). Then, given a network of genes or proteins and similarity values between some of them, we seek connected sub-networks (or modules) that manifest high similarity. We develop algorithms for this problem and evaluate their performance on the osmotic shock response network in S. cerevisiae and on the human cell cycle network. We demonstrate that focused, biologically meaningful and relevant functional modules are obtained. In comparison with extant algorithms, our approach has higher sensitivity and higher specificity. We have demonstrated that our method can accurately identify functional modules. Hence, it carries the promise to be highly useful in analysis of high throughput data.

An autonomous molecular computer for logical control of gene expression

PubMed Central

Benenson, Yaakov; Gil, Binyamin; Ben-Dor, Uri; Adar, Rivka; Shapiro, Ehud

2013-01-01

Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems1–7. Recently, simple molecular-scale autonomous programmable computers were demonstrated8–15 allowing both input and output information to be in molecular form. Such computers, using biological molecules as input data and biologically active molecules as outputs, could produce a system for ‘logical’ control of biological processes. Here we describe an autonomous biomolecular computer that, at least in vitro, logically analyses the levels of messenger RNA species, and in response produces a molecule capable of affecting levels of gene expression. The computer operates at a concentration of close to a trillion computers per microlitre and consists of three programmable modules: a computation module, that is, a stochastic molecular automaton12–17; an input module, by which specific mRNA levels or point mutations regulate software molecule concentrations, and hence automaton transition probabilities; and an output module, capable of controlled release of a short single-stranded DNA molecule. This approach might be applied in vivo to biochemical sensing, genetic engineering and even medical diagnosis and treatment. As a proof of principle we programmed the computer to identify and analyse mRNA of disease-related genes18–22 associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modelled after an anticancer drug. PMID:15116117

De Anza Summer College "By the Sea"; Evaluation Report, 1974.

ERIC Educational Resources Information Center

College of the Redwoods, Eureka, CA.

This report describes an off-campus alternative to traditional summer school sponsored by De Anza College and College of the Redwoods (California). Three twelve-day, concentrated summer programs, called "Action Learning Modules", utilized an interdisciplinary approach. The first module combined oceanography, marine biology, and scuba diving. A…

Project Solo; Newsletter Number Seven.

ERIC Educational Resources Information Center

Pittsburgh Univ., PA. Project Solo.

The current curriculum modules under development at Project Solo are listed. The modules are grouped under the subject matter that they are designed to teach--algebra II, biology, calculus, chemistry, computer science, 12th grade math, physics, social science. Special programs written for use on the Hewlett-Packard Plotter are listed that may be…

Frequency modulation atomic force microscopy: a dynamic measurement technique for biological systems

NASA Astrophysics Data System (ADS)

Higgins, Michael J.; Riener, Christian K.; Uchihashi, Takayuki; Sader, John E.; McKendry, Rachel; Jarvis, Suzanne P.

2005-03-01

Frequency modulation atomic force microscopy (FM-AFM) has been modified to operate in a liquid environment within an atomic force microscope specifically designed for investigating biological samples. We demonstrate the applicability of FM-AFM to biological samples using the spectroscopy mode to measure the unbinding forces of a single receptor-ligand (biotin-avidin) interaction. We show that quantitative adhesion force measurements can only be obtained provided certain modifications are made to the existing theory, which is used to convert the detected frequency shifts to an interaction force. Quantitative force measurements revealed that the unbinding forces for the biotin-avidin interaction were greater than those reported in previous studies. This finding was due to the use of high average tip velocities, which were calculated to be two orders of magnitude greater than those typically used in unbinding receptor-ligand experiments. This study therefore highlights the potential use of FM-AFM to study a range of biological systems, including living cells and/or single biomolecule interactions.

Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology.

PubMed

Wang, Baojun; Kitney, Richard I; Joly, Nicolas; Buck, Martin

2011-10-18

Modular and orthogonal genetic logic gates are essential for building robust biologically based digital devices to customize cell signalling in synthetic biology. Here we constructed an orthogonal AND gate in Escherichia coli using a novel hetero-regulation module from Pseudomonas syringae. The device comprises two co-activating genes hrpR and hrpS controlled by separate promoter inputs, and a σ(54)-dependent hrpL promoter driving the output. The hrpL promoter is activated only when both genes are expressed, generating digital-like AND integration behaviour. The AND gate is demonstrated to be modular by applying new regulated promoters to the inputs, and connecting the output to a NOT gate module to produce a combinatorial NAND gate. The circuits were assembled using a parts-based engineering approach of quantitative characterization, modelling, followed by construction and testing. The results show that new genetic logic devices can be engineered predictably from novel native orthogonal biological control elements using quantitatively in-context characterized parts. © 2011 Macmillan Publishers Limited. All rights reserved.

Systems and methods for detecting and processing

DOEpatents

Johnson, Michael M [Livermore, CA; Yoshimura, Ann S [Tracy, CA

2006-03-28

Embodiments of the present invention provides systems and method for detecting. Sensing modules are provided in communication with one or more detectors. In some embodiments, detectors are provided that are sensitive to chemical, biological, or radiological agents. Embodiments of sensing modules include processing capabilities to analyze, perform computations on, and/or run models to predict or interpret data received from one or more detectors. Embodiments of sensing modules form various network configurations with one another and/or with one or more data aggregation devices. Some embodiments of sensing modules include power management functionalities.

Modular analysis of biological networks.

PubMed

Kaltenbach, Hans-Michael; Stelling, Jörg

2012-01-01

The analysis of complex biological networks has traditionally relied on decomposition into smaller, semi-autonomous units such as individual signaling pathways. With the increased scope of systems biology (models), rational approaches to modularization have become an important topic. With increasing acceptance of de facto modularity in biology, widely different definitions of what constitutes a module have sparked controversies. Here, we therefore review prominent classes of modular approaches based on formal network representations. Despite some promising research directions, several important theoretical challenges remain open on the way to formal, function-centered modular decompositions for dynamic biological networks.

Apoptotic cell death during Drosophila oogenesis is differentially increased by electromagnetic radiation depending on modulation, intensity and duration of exposure.

PubMed

Sagioglou, Niki E; Manta, Areti K; Giannarakis, Ioannis K; Skouroliakou, Aikaterini S; Margaritis, Lukas H

2016-01-01

Present generations are being repeatedly exposed to different types and doses of non-ionizing radiation (NIR) from wireless technologies (FM radio, TETRA and TV stations, GSM and UMTS phones/base stations, Wi-Fi networks, DECT phones). Although there is controversy on the published data regarding the non-thermal effects of NIR, studies have convincingly demonstrated bioeffects. Their results indicate that modulation, intensity, exposure duration and model system are important factors determining the biological response to irradiation. Attempting to address the dependence of NIR bioeffectiveness on these factors, apoptosis in the model biological system Drosophila melanogaster was studied under different exposure protocols. A signal generator was used operating alternatively under Continuous Wave (CW) or Frequency Modulation (FM) emission modes, at three power output values (10 dB, 0, -10 dB), under four carrier frequencies (100, 395, 682, 900 MHz). Newly emerged flies were exposed either acutely (6 min or 60 min on the 6th day), or repeatedly (6 min or 60 min daily for the first 6 days of their life). All exposure protocols resulted in an increase of apoptotic cell death (ACD) observed in egg chambers, even at very low electric field strengths. FM waves seem to have a stronger effect in ACD than continuous waves. Regarding intensity and temporal exposure pattern, EMF-biological tissue interaction is not linear in response. Intensity threshold for the induction of biological effects depends on frequency, modulation and temporal exposure pattern with unknown so far mechanisms. Given this complexity, translating such experimental data into possible human exposure guidelines is yet arbitrary.

Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease.

PubMed

Modena, Brian D; Bleecker, Eugene R; Busse, William W; Erzurum, Serpil C; Gaston, Benjamin M; Jarjour, Nizar N; Meyers, Deborah A; Milosevic, Jadranka; Tedrow, John R; Wu, Wei; Kaminski, Naftali; Wenzel, Sally E

2017-06-01

Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Identify networks of genes reflective of underlying biological processes that define SA. Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12-21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes.

Gene Expression Correlated with Severe Asthma Characteristics Reveals Heterogeneous Mechanisms of Severe Disease

PubMed Central

Modena, Brian D.; Bleecker, Eugene R.; Busse, William W.; Erzurum, Serpil C.; Gaston, Benjamin M.; Jarjour, Nizar N.; Meyers, Deborah A.; Milosevic, Jadranka; Tedrow, John R.; Wu, Wei; Kaminski, Naftali

2017-01-01

Rationale: Severe asthma (SA) is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of bronchial epithelial cells in individuals with asthma have provided biological insight and underscored possible mechanistic differences between individuals. Objectives: Identify networks of genes reflective of underlying biological processes that define SA. Methods: Airway epithelial cell gene expression from 155 subjects with asthma and healthy control subjects in the Severe Asthma Research Program was analyzed by weighted gene coexpression network analysis to identify gene networks and profiles associated with SA and its specific characteristics (i.e., pulmonary function tests, quality of life scores, urgent healthcare use, and steroid use), which potentially identified underlying biological processes. A linear model analysis confirmed these findings while adjusting for potential confounders. Measurements and Main Results: Weighted gene coexpression network analysis constructed 64 gene network modules, including modules corresponding to T1 and T2 inflammation, neuronal function, cilia, epithelial growth, and repair mechanisms. Although no network selectively identified SA, genes in modules linked to epithelial growth and repair and neuronal function were markedly decreased in SA. Several hub genes of the epithelial growth and repair module were found located at the 17q12–21 locus, near a well-known asthma susceptibility locus. T2 genes increased with severity in those treated with corticosteroids but were also elevated in untreated, mild-to-moderate disease compared with healthy control subjects. T1 inflammation, especially when associated with increased T2 gene expression, was elevated in a subgroup of younger patients with SA. Conclusions: In this hypothesis-generating analysis, gene expression networks in relation to asthma severity provided potentially new insight into biological mechanisms associated with the development of SA and its phenotypes. PMID:27984699

Integrative Analysis of Many Weighted Co-Expression Networks Using Tensor Computation

PubMed Central

Li, Wenyuan; Liu, Chun-Chi; Zhang, Tong; Li, Haifeng; Waterman, Michael S.; Zhou, Xianghong Jasmine

2011-01-01

The rapid accumulation of biological networks poses new challenges and calls for powerful integrative analysis tools. Most existing methods capable of simultaneously analyzing a large number of networks were primarily designed for unweighted networks, and cannot easily be extended to weighted networks. However, it is known that transforming weighted into unweighted networks by dichotomizing the edges of weighted networks with a threshold generally leads to information loss. We have developed a novel, tensor-based computational framework for mining recurrent heavy subgraphs in a large set of massive weighted networks. Specifically, we formulate the recurrent heavy subgraph identification problem as a heavy 3D subtensor discovery problem with sparse constraints. We describe an effective approach to solving this problem by designing a multi-stage, convex relaxation protocol, and a non-uniform edge sampling technique. We applied our method to 130 co-expression networks, and identified 11,394 recurrent heavy subgraphs, grouped into 2,810 families. We demonstrated that the identified subgraphs represent meaningful biological modules by validating against a large set of compiled biological knowledge bases. We also showed that the likelihood for a heavy subgraph to be meaningful increases significantly with its recurrence in multiple networks, highlighting the importance of the integrative approach to biological network analysis. Moreover, our approach based on weighted graphs detects many patterns that would be overlooked using unweighted graphs. In addition, we identified a large number of modules that occur predominately under specific phenotypes. This analysis resulted in a genome-wide mapping of gene network modules onto the phenome. Finally, by comparing module activities across many datasets, we discovered high-order dynamic cooperativeness in protein complex networks and transcriptional regulatory networks. PMID:21698123

Full Monte Carlo-Based Biologic Treatment Plan Optimization System for Intensity Modulated Carbon Ion Therapy on Graphics Processing Unit.

PubMed

Qin, Nan; Shen, Chenyang; Tsai, Min-Yu; Pinto, Marco; Tian, Zhen; Dedes, Georgios; Pompos, Arnold; Jiang, Steve B; Parodi, Katia; Jia, Xun

2018-01-01

One of the major benefits of carbon ion therapy is enhanced biological effectiveness at the Bragg peak region. For intensity modulated carbon ion therapy (IMCT), it is desirable to use Monte Carlo (MC) methods to compute the properties of each pencil beam spot for treatment planning, because of their accuracy in modeling physics processes and estimating biological effects. We previously developed goCMC, a graphics processing unit (GPU)-oriented MC engine for carbon ion therapy. The purpose of the present study was to build a biological treatment plan optimization system using goCMC. The repair-misrepair-fixation model was implemented to compute the spatial distribution of linear-quadratic model parameters for each spot. A treatment plan optimization module was developed to minimize the difference between the prescribed and actual biological effect. We used a gradient-based algorithm to solve the optimization problem. The system was embedded in the Varian Eclipse treatment planning system under a client-server architecture to achieve a user-friendly planning environment. We tested the system with a 1-dimensional homogeneous water case and 3 3-dimensional patient cases. Our system generated treatment plans with biological spread-out Bragg peaks covering the targeted regions and sparing critical structures. Using 4 NVidia GTX 1080 GPUs, the total computation time, including spot simulation, optimization, and final dose calculation, was 0.6 hour for the prostate case (8282 spots), 0.2 hour for the pancreas case (3795 spots), and 0.3 hour for the brain case (6724 spots). The computation time was dominated by MC spot simulation. We built a biological treatment plan optimization system for IMCT that performs simulations using a fast MC engine, goCMC. To the best of our knowledge, this is the first time that full MC-based IMCT inverse planning has been achieved in a clinically viable time frame. Copyright © 2017 Elsevier Inc. All rights reserved.

Photoacoustic resonance spectroscopy for biological tissue characterization

NASA Astrophysics Data System (ADS)

Gao, Fei; Feng, Xiaohua; Zheng, Yuanjin; Ohl, Claus-Dieter

2014-06-01

By "listening to photons," photoacoustics allows the probing of chromosomes in depth beyond the optical diffusion limit. Here we report the photoacoustic resonance effect induced by multiburst modulated laser illumination, which is theoretically modeled as a damped mass-string oscillator and a resistor-inductor-capacitor (RLC) circuit. Through sweeping the frequency of multiburst modulated laser, the photoacoustic resonance effect is observed experimentally on phantoms and porcine tissues. Experimental results demonstrate different spectra for each phantom and tissue sample to show significant potential for spectroscopic analysis, fusing optical absorption and mechanical vibration properties. Unique RLC circuit parameters are extracted to quantitatively characterize phantom and biological tissues.

clusterProfiler: an R package for comparing biological themes among gene clusters.

PubMed

Yu, Guangchuang; Wang, Li-Gen; Han, Yanyan; He, Qing-Yu

2012-05-01

Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.

Discovery and validation of a glioblastoma co-expressed gene module

PubMed Central

Dunwoodie, Leland J.; Poehlman, William L.; Ficklin, Stephen P.; Feltus, Frank Alexander

2018-01-01

Tumors exhibit complex patterns of aberrant gene expression. Using a knowledge-independent, noise-reducing gene co-expression network construction software called KINC, we created multiple RNAseq-based gene co-expression networks relevant to brain and glioblastoma biology. In this report, we describe the discovery and validation of a glioblastoma-specific gene module that contains 22 co-expressed genes. The genes are upregulated in glioblastoma relative to normal brain and lower grade glioma samples; they are also hypo-methylated in glioblastoma relative to lower grade glioma tumors. Among the proneural, neural, mesenchymal, and classical glioblastoma subtypes, these genes are most-highly expressed in the mesenchymal subtype. Furthermore, high expression of these genes is associated with decreased survival across each glioblastoma subtype. These genes are of interest to glioblastoma biology and our gene interaction discovery and validation workflow can be used to discover and validate co-expressed gene modules derived from any co-expression network. PMID:29541392

Discovery and validation of a glioblastoma co-expressed gene module.

PubMed

Dunwoodie, Leland J; Poehlman, William L; Ficklin, Stephen P; Feltus, Frank Alexander

2018-02-16

Tumors exhibit complex patterns of aberrant gene expression. Using a knowledge-independent, noise-reducing gene co-expression network construction software called KINC, we created multiple RNAseq-based gene co-expression networks relevant to brain and glioblastoma biology. In this report, we describe the discovery and validation of a glioblastoma-specific gene module that contains 22 co-expressed genes. The genes are upregulated in glioblastoma relative to normal brain and lower grade glioma samples; they are also hypo-methylated in glioblastoma relative to lower grade glioma tumors. Among the proneural, neural, mesenchymal, and classical glioblastoma subtypes, these genes are most-highly expressed in the mesenchymal subtype. Furthermore, high expression of these genes is associated with decreased survival across each glioblastoma subtype. These genes are of interest to glioblastoma biology and our gene interaction discovery and validation workflow can be used to discover and validate co-expressed gene modules derived from any co-expression network.

Early sex-specific modulation of the molecular clock in trauma.

PubMed

Mehraj, Vikram; Wiramus, Sandrine; Capo, Christian; Leone, Marc; Mege, Jean-Louis; Textoris, Julien

2014-01-01

Immune system biology and most physiologic functions are tightly linked to circadian rhythms. Time of day-dependent variations in many biologic parameters also play a fundamental role in the disease process. We previously showed that the genes encoding the peripheral molecular clock were modulated in a sex-dependent manner in Q fever. Here, we examined severe trauma patients at admission to the intensive care unit. Using quantitative real-time polymerase chain reaction, the whole-blood expression of the molecular clock components ARNTL, CLOCK, and PER2 was assessed in male and female trauma patients. Healthy volunteers of both sexes were used as controls. We observed a significant overexpression of both ARNTL and CLOCK in male trauma patients. We report, for the first time, the sex-related modulation of the molecular clock genes in the blood following severe trauma. These results emphasize the role of circadian rhythms in the immune response in trauma patients. Epidemiologic study, level IV.

A new modulated Hebbian learning rule--biologically plausible method for local computation of a principal subspace.

PubMed

Jankovic, Marko; Ogawa, Hidemitsu

2003-08-01

This paper presents one possible implementation of a transformation that performs linear mapping to a lower-dimensional subspace. Principal component subspace will be the one that will be analyzed. Idea implemented in this paper represents generalization of the recently proposed infinity OH neural method for principal component extraction. The calculations in the newly proposed method are performed locally--a feature which is usually considered as desirable from the biological point of view. Comparing to some other wellknown methods, proposed synaptic efficacy learning rule requires less information about the value of the other efficacies to make single efficacy modification. Synaptic efficacies are modified by implementation of Modulated Hebb-type (MH) learning rule. Slightly modified MH algorithm named Modulated Hebb Oja (MHO) algorithm, will be also introduced. Structural similarity of the proposed network with part of the retinal circuit will be presented, too.

Direct Modulation of Heterotrimeric G Protein-coupled Signaling by a Receptor Kinase Complex.

PubMed

Tunc-Ozdemir, Meral; Urano, Daisuke; Jaiswal, Dinesh Kumar; Clouse, Steven D; Jones, Alan M

2016-07-01

Plants and some protists have heterotrimeric G protein complexes that activate spontaneously without canonical G protein-coupled receptors (GPCRs). In Arabidopsis, the sole 7-transmembrane regulator of G protein signaling 1 (AtRGS1) modulates the G protein complex by keeping it in the resting state (GDP-bound). However, it remains unknown how a myriad of biological responses is achieved with a single G protein modulator. We propose that in complete contrast to G protein activation in animals, plant leucine-rich repeat receptor-like kinases (LRR RLKs), not GPCRs, provide this discrimination through phosphorylation of AtRGS1 in a ligand-dependent manner. G protein signaling is directly activated by the pathogen-associated molecular pattern flagellin peptide 22 through its LRR RLK, FLS2, and co-receptor BAK1. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

RE-PLAN: An Extensible Software Architecture to Facilitate Disaster Response Planning

PubMed Central

O’Neill, Martin; Mikler, Armin R.; Indrakanti, Saratchandra; Tiwari, Chetan; Jimenez, Tamara

2014-01-01

Computational tools are needed to make data-driven disaster mitigation planning accessible to planners and policymakers without the need for programming or GIS expertise. To address this problem, we have created modules to facilitate quantitative analyses pertinent to a variety of different disaster scenarios. These modules, which comprise the REsponse PLan ANalyzer (RE-PLAN) framework, may be used to create tools for specific disaster scenarios that allow planners to harness large amounts of disparate data and execute computational models through a point-and-click interface. Bio-E, a user-friendly tool built using this framework, was designed to develop and analyze the feasibility of ad hoc clinics for treating populations following a biological emergency event. In this article, the design and implementation of the RE-PLAN framework are described, and the functionality of the modules used in the Bio-E biological emergency mitigation tool are demonstrated. PMID:25419503

Gel integration for microfluidic applications.

PubMed

Zhang, Xuanqi; Li, Lingjun; Luo, Chunxiong

2016-05-21

Molecular diffusive membranes or materials are important for biological applications in microfluidic systems. Hydrogels are typical materials that offer several advantages, such as free diffusion for small molecules, biocompatibility with most cells, temperature sensitivity, relatively low cost, and ease of production. With the development of microfluidic applications, hydrogels can be integrated into microfluidic systems by soft lithography, flow-solid processes or UV cure methods. Due to their special properties, hydrogels are widely used as fluid control modules, biochemical reaction modules or biological application modules in different applications. Although hydrogels have been used in microfluidic systems for more than ten years, many hydrogels' properties and integrated techniques have not been carefully elaborated. Here, we systematically review the physical properties of hydrogels, general methods for gel-microfluidics integration and applications of this field. Advanced topics and the outlook of hydrogel fabrication and applications are also discussed. We hope this review can help researchers choose suitable methods for their applications using hydrogels.

Mode-locking via dissipative Faraday instability

PubMed Central

Tarasov, Nikita; Perego, Auro M.; Churkin, Dmitry V.; Staliunas, Kestutis; Turitsyn, Sergei K.

2016-01-01

Emergence of coherent structures and patterns at the nonlinear stage of modulation instability of a uniform state is an inherent feature of many biological, physical and engineering systems. There are several well-studied classical modulation instabilities, such as Benjamin–Feir, Turing and Faraday instability, which play a critical role in the self-organization of energy and matter in non-equilibrium physical, chemical and biological systems. Here we experimentally demonstrate the dissipative Faraday instability induced by spatially periodic zig-zag modulation of a dissipative parameter of the system—spectrally dependent losses—achieving generation of temporal patterns and high-harmonic mode-locking in a fibre laser. We demonstrate features of this instability that distinguish it from both the Benjamin–Feir and the purely dispersive Faraday instability. Our results open the possibilities for new designs of mode-locked lasers and can be extended to other fields of physics and engineering. PMID:27503708

Mode-locking via dissipative Faraday instability.

PubMed

Tarasov, Nikita; Perego, Auro M; Churkin, Dmitry V; Staliunas, Kestutis; Turitsyn, Sergei K

2016-08-09

Emergence of coherent structures and patterns at the nonlinear stage of modulation instability of a uniform state is an inherent feature of many biological, physical and engineering systems. There are several well-studied classical modulation instabilities, such as Benjamin-Feir, Turing and Faraday instability, which play a critical role in the self-organization of energy and matter in non-equilibrium physical, chemical and biological systems. Here we experimentally demonstrate the dissipative Faraday instability induced by spatially periodic zig-zag modulation of a dissipative parameter of the system-spectrally dependent losses-achieving generation of temporal patterns and high-harmonic mode-locking in a fibre laser. We demonstrate features of this instability that distinguish it from both the Benjamin-Feir and the purely dispersive Faraday instability. Our results open the possibilities for new designs of mode-locked lasers and can be extended to other fields of physics and engineering.

Active ingredients of ginger as potential candidates in the prevention and treatment of diseases via modulation of biological activities

PubMed Central

Rahmani, Arshad H; shabrmi, Fahad M Al; Aly, Salah M

2014-01-01

The current mode of treatment based on synthetic drugs is expensive and also causes genetic and metabolic alterations. However, safe and sound mode of treatment is needed to control the diseases development and progression. In this regards, medicinal plant and its constituents play an important role in diseases management via modulation of biological activities. Ginger, the rhizome of the Zingiber officinale, has shown therapeutic role in the health management since ancient time and considered as potential chemopreventive agent. Numerous studies based on clinical trials and animal model has shown that ginger and its constituents shows significant role in the prevention of diseases via modulation of genetic and metabolic activities. In this review, we focused on the therapeutics effects of ginger and its constituents in the diseases management, and its impact on genetic and metabolic activities. PMID:25057339

Problem-Solving Modules in Large Introductory Biology Lectures Enhance Student Understanding

ERIC Educational Resources Information Center

Cooper, Scott; Hanmer, Deborah; Cerbin, Bill

2006-01-01

We studied the effect of formative assessment and feedback on learning. Students produced phylogenetic trees based upon morphological and molecular data. The trees were projected in class, feedback provided, and the process repeated twice with new data. Assessment revealed that these in-class modules resulted in significant improvement in student…

Wound induces changes in nitric oxide related biologies putatively modulating tuber healing

USDA-ARS?s Scientific Manuscript database

Wound-related losses in harvested potatoes and cut seed are a serious and costly problem (losses > $320 m/yr). Our understanding of the regulation and modulation of the processes involved in wound healing (WH) are advancing and showing promise in the development of new approaches and technologies t...

A Compulsory Bioethics Module for a Large Final Year Undergraduate Class

ERIC Educational Resources Information Center

Pearce, Roger S.

2009-01-01

The article describes a compulsory bioethics module delivered to [approximately] 120 biology students in their final year. The main intended learning outcome is that students should be able to analyse and reason about bioethical issues. Interactive lectures explain and illustrate bioethics. Underlying principles and example issues are used to…

Supporting Student Learning: The Use of Computer-Based Formative Assessment Modules.

ERIC Educational Resources Information Center

Peat, Mary; Franklin, Sue

2002-01-01

Describes the development of a variety of computer-based assessment opportunities, both formative and summative, that are available to a large first-year biology class at the University of Sydney (Australia). Discusses online access to weekly quizzes, a mock exam, and special self-assessment modules that are beneficial to student learning.…

Land Application of Wastes: An Educational Program. Waste Characteristics - Module 5, Objectives, and Script.

ERIC Educational Resources Information Center

Clarkson, W. W.; And Others

This module introduces the physical, biological, and chemical constituents of wastewaters and sludges which are of concern in land treatment systems. The characteristics of typical municipal wastewater are tabulated for strong, medium, and weak sewages. Some of the factors affecting pollutant concentrations are listed. Flow, distribution and…

The glutathione-S-transferase mu 1 (GSTM1) null genotype and increased neutrophil response to low-level ozone (0.06 ppm).

EPA Science Inventory

Background: Exposure of healthy young adults to 03 modulates immune cell biology in the airways and causes a significant increase in neutrophilic inflammation which can vary considerably in magnitude across individuals. The GSTM1null genotype modulates Oj-induced inflammation, bu...

Prostanoids and their receptors that modulate dendritic cell-mediated immunity.

PubMed

Gualde, Norbert; Harizi, Hedi

2004-08-01

Dendritic cells (DC) are essential for the initiation of immune responses by capturing, processing and presenting antigens to T cells. In addition to their important role as professional APC, they are able to produce immunosuppressive and pro-inflammatory prostanoids from arachidonic acid (AA) by the action of cyclooxygenase (COX) enzymes. In an autocrine and paracrine fashion, the secreted lipid mediators subsequently modulate the maturation, cytokine production, Th-cell polarizing ability, chemokine receptor expression, migration, and apoptosis of these extremely versatile APC. The biological actions of prostanoids, including their effects on APC-mediated immunity and acute inflammatory responses, are exerted by G protein-coupled receptors on plasma membrane. Some COX metabolites act as anti-inflammatory lipid mediators by binding to nuclear receptors and modulating DC functions. Although the role of cytokines in DC function has been studied extensively, the effects of prostanoids on DC biology have only recently become the focus of investigation. This review summarizes the current knowledge about the role of prostanoids and their receptors in modulating DC function and the subsequent immune responses.

BIOLOGICAL INFLUENCES OF LOW-FREQUENCY SINUSOIDAL ELECTROMAGNETIC SIGNALS ALONE AND SUPERIMPOSED ON RF CARRIER WAVES

EPA Science Inventory

The report describes in a historical context the experiments that have been performed to examine the biological responses caused by exposure to low frequency electromagnetic radiation directly or as modulation of RF carrier waves. A detailed review is provided of the independentl...

Integrating Introductory Biology and General Chemistry Laboratories.

ERIC Educational Resources Information Center

Godrick, Elizabeth; Hartman, Standish

2000-01-01

Introduces a science laboratory integrating biology and chemistry courses that includes four modules: (1) the fundamental process of reactions; (2) a semester-long project on the chemical assay of ascorbic acid; (3) human metabolism of Vitamin C; and (4) an open-ended project on the manipulation of macromolecules. (YDS)

An Open-Ended Investigative Microbial Ecology Laboratory for Introductory Biology

ERIC Educational Resources Information Center

Jones-Held, Susan; Paoletti, Robert; Glick, David; Held, Michael E.

2010-01-01

In this article we describe a multi-week investigative laboratory in microbial ecology/diversity and nitrogen cycling that we have used in our introductory biology course. This module encourages active student involvement in experimental design, using the scientific literature and quantitative analysis of large data sets. Students analyze soil…

A photoelastic modulator-based birefringence imaging microscope for measuring biological specimens

NASA Astrophysics Data System (ADS)

Freudenthal, John; Leadbetter, Andy; Wolf, Jacob; Wang, Baoliang; Segal, Solomon

2014-11-01

The photoelastic modulator (PEM) has been applied to a variety of polarimetric measurements. However, nearly all such applications use point-measurements where each point (spot) on the sample is measured one at a time. The main challenge for employing the PEM in a camera-based imaging instrument is that the PEM modulates too fast for typical cameras. The PEM modulates at tens of KHz. To capture the specific polarization information that is carried on the modulation frequency of the PEM, the camera needs to be at least ten times faster. However, the typical frame rates of common cameras are only in the tens or hundreds frames per second. In this paper, we report a PEM-camera birefringence imaging microscope. We use the so-called stroboscopic illumination method to overcome the incompatibility of the high frequency of the PEM to the relatively slow frame rate of a camera. We trigger the LED light source using a field-programmable gate array (FPGA) in synchrony with the modulation of the PEM. We show the measurement results of several standard birefringent samples as a part of the instrument calibration. Furthermore, we show results observed in two birefringent biological specimens, a human skin tissue that contains collagen and a slice of mouse brain that contains bundles of myelinated axonal fibers. Novel applications of this PEM-based birefringence imaging microscope to both research communities and industrial applications are being tested.

From protein-protein interactions to protein co-expression networks: a new perspective to evaluate large-scale proteomic data.

PubMed

Vella, Danila; Zoppis, Italo; Mauri, Giancarlo; Mauri, Pierluigi; Di Silvestre, Dario

2017-12-01

The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory. Genomic and proteomic data are often combined with protein-protein interaction (PPI) networks whose structure is routinely analyzed by algorithms and tools to characterize hubs/bottlenecks and topological, functional, and disease modules. On the other hand, co-expression networks represent a complementary procedure that give the opportunity to evaluate at system level including organisms that lack information on PPIs. Based on these premises, we introduce the reader to the PPI and to the co-expression networks, including aspects of reconstruction and analysis. In particular, the new idea to evaluate large-scale proteomic data by means of co-expression networks will be discussed presenting some examples of application. Their use to infer biological knowledge will be shown, and a special attention will be devoted to the topological and module analysis.

Optically modulated fluorescence bioimaging: visualizing obscured fluorophores in high background.

PubMed

Hsiang, Jung-Cheng; Jablonski, Amy E; Dickson, Robert M

2014-05-20

Fluorescence microscopy and detection have become indispensible for understanding organization and dynamics in biological systems. Novel fluorophores with improved brightness, photostability, and biocompatibility continue to fuel further advances but often rely on having minimal background. The visualization of interactions in very high biological background, especially for proteins or bound complexes at very low copy numbers, remains a primary challenge. Instead of focusing on molecular brightness of fluorophores, we have adapted the principles of high-sensitivity absorption spectroscopy to improve the sensitivity and signal discrimination in fluorescence bioimaging. Utilizing very long wavelength transient absorptions of kinetically trapped dark states, we employ molecular modulation schemes that do not simultaneously modulate the background fluorescence. This improves the sensitivity and ease of implementation over high-energy photoswitch-based recovery schemes, as no internal dye reference or nanoparticle-based fluorophores are needed to separate the desired signals from background. In this Account, we describe the selection process for and identification of fluorophores that enable optically modulated fluorescence to decrease obscuring background. Differing from thermally stable photoswitches using higher-energy secondary lasers, coillumination at very low energies depopulates transient dark states, dynamically altering the fluorescence and giving characteristic modulation time scales for each modulatable emitter. This process is termed synchronously amplified fluorescence image recovery (SAFIRe) microscopy. By understanding and optically controlling the dye photophysics, we selectively modulate desired fluorophore signals independent of all autofluorescent background. This shifts the fluorescence of interest to unique detection frequencies with nearly shot-noise-limited detection, as no background signals are collected. Although the fluorescence brightness is improved slightly, SAFIRe yields up to 100-fold improved signal visibility by essentially removing obscuring, unmodulated background (Richards, C. I.; J. Am. Chem. Soc. 2009, 131, 4619). While SAFIRe exhibits a wide, linear dynamic range, we have demonstrated single-molecule signal recovery buried within 200 nM obscuring dye. In addition to enabling signal recovery through background reduction, each dye exhibits a characteristic modulation frequency indicative of its photophysical dynamics. Thus, these characteristic time scales offer opportunities not only to expand the dimensionality of fluorescence imaging by using dark-state lifetimes but also to distinguish the dynamics of subpopulations on the basis of photophysical versus diffusional time scales, even within modulatable populations. The continued development of modulation for signal recovery and observation of biological dynamics holds great promise for studying a range of transient biological phenomena in natural environments. Through the development of a wide range of fluorescent proteins, organic dyes, and inorganic emitters that exhibit significant dark-state populations under steady-state illumination, we can drastically expand the applicability of fluorescence imaging to probe lower-abundance complexes and their dynamics.

Environmental and biological context modulates the physiological stress response of bats to human disturbance.

PubMed

Phelps, Kendra L; Kingston, Tigga

2018-06-01

Environmental and biological context play significant roles in modulating physiological stress responses of individuals in wildlife populations yet are often overlooked when evaluating consequences of human disturbance on individual health and fitness. Furthermore, most studies gauge individual stress responses based on a single physiological biomarker, typically circulating glucocorticoid concentrations, which limits interpretation of the complex, multifaceted responses of individuals to stressors. We selected four physiological biomarkers to capture short-term and prolonged stress responses in a widespread cave-roosting bat, Hipposideros diadema, across multiple gradients of human disturbance in and around caves in the Philippines. We used conditional inference trees and random forest analysis to determine the role of environmental quality (cave complexity, available roosting area), assemblage composition (intra- and interspecific associations and species richness), and intrinsic characteristics of individuals (sex and reproductive status) in modulating responses to disturbance. Direct cave disturbance (hunting pressure and human visitation) was the primary driver of neutrophil-to-lymphocyte ratios, with lower ratios associated with increased disturbance, while context-specific factors were more important in explaining total leukocyte count, body condition, and ectoparasite load. Moreover, conditional inference trees revealed complex interactions among human disturbance and modulating factors. Cave complexity often ameliorated individual responses to human disturbance, whereas conspecific abundance often compounded responses. Our study demonstrates the importance of an integrated approach that incorporates environmental and biological context when identifying drivers of physiological responses, and that assesses responses to gradients of direct and indirect disturbance using multiple complementary biomarkers.

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module.

PubMed

McIlrath, Victoria; Trye, Alice; Aguanno, Ann

2015-06-18

Undergraduate biology students are required to learn, understand and apply a variety of cellular and molecular biology concepts and techniques in preparation for biomedical, graduate and professional programs or careers in science. To address this, a simple laboratory module was devised to teach the concepts of cell division, cellular communication and cancer through the application of animal cell culture techniques. Here the mouse mammary tumor (MMT) cell line is used to model for breast cancer. Students learn to grow and characterize these animal cells in culture and test the effects of traditional and non-traditional chemotherapy agents on cell proliferation. Specifically, students determine the optimal cell concentration for plating and growing cells, learn how to prepare and dilute drug solutions, identify the best dosage and treatment time course of the antiproliferative agents, and ascertain the rate of cell death in response to various treatments. The module employs both a standard cell counting technique using a hemocytometer and a novel cell counting method using microscopy software. The experimental procedure lends to open-ended inquiry as students can modify critical steps of the protocol, including testing homeopathic agents and over-the-counter drugs. In short, this lab module requires students to use the scientific process to apply their knowledge of the cell cycle, cellular signaling pathways, cancer and modes of treatment, all while developing an array of laboratory skills including cell culture and analysis of experimental data not routinely taught in the undergraduate classroom.

Designing Online Resources in Preparation for Authentic Laboratory Experiences

PubMed Central

Boulay, Rachel; Parisky, Alex; Leong, Peter

2013-01-01

Professional development for science teachers can be benefited through active learning in science laboratories. However, how online training materials can be used to complement traditional laboratory training is less understood. This paper explores the design of online training modules to teach molecular biology and user perception of those modules that were part of an intensive molecular biology “boot camp” targeting high school biology teachers in the State of Hawaii. The John A. Burns School of Medicine at the University of Hawaii had an opportunity to design and develop professional development that prepares science teachers with an introduction of skills, techniques, and applications for their students to conduct medical research in a laboratory setting. A group of 29 experienced teachers shared their opinions of the online materials and reported on how they used the online materials in their learning process or teaching. PMID:24319698

Development and verification of hardware for life science experiments in the Japanese Experiment Module "Kibo" on the International Space Station.

PubMed

Ishioka, Noriaki; Suzuki, Hiromi; Asashima, Makoto; Kamisaka, Seiichiro; Mogami, Yoshihiro; Ochiai, Toshimasa; Aizawa-Yano, Sachiko; Higashibata, Akira; Ando, Noboru; Nagase, Mutsumu; Ogawa, Shigeyuki; Shimazu, Toru; Fukui, Keiji; Fujimoto, Nobuyoshi

2004-03-01

Japan Aerospace Exploration Agency (JAXA) has developed a cell biology experiment facility (CBEF) and a clean bench (CB) as a common hardware in which life science experiments in the Japanese Experiment Module (JEM known as "Kibo") of the International Space Station (ISS) can be performed. The CBEF, a CO2 incubator with a turntable that provides variable gravity levels, is the basic hardware required to carry out the biological experiments using microorganisms, cells, tissues, small animals, plants, etc. The CB provides a closed aseptic operation area for life science and biotechnology experiments in Kibo. A phase contrast and fluorescence microscope is installed inside CB. The biological experiment units (BEU) are designed to run individual experiments using the CBEF and the CB. A plant experiment unit (PEU) and two cell experiment units (CEU type1 and type2) for the BEU have been developed.

Cell illustrator 4.0: a computational platform for systems biology.

PubMed

Nagasaki, Masao; Saito, Ayumu; Jeong, Euna; Li, Chen; Kojima, Kaname; Ikeda, Emi; Miyano, Satoru

2011-01-01

Cell Illustrator is a software platform for Systems Biology that uses the concept of Petri net for modeling and simulating biopathways. It is intended for biological scientists working at bench. The latest version of Cell Illustrator 4.0 uses Java Web Start technology and is enhanced with new capabilities, including: automatic graph grid layout algorithms using ontology information; tools using Cell System Markup Language (CSML) 3.0 and Cell System Ontology 3.0; parameter search module; high-performance simulation module; CSML database management system; conversion from CSML model to programming languages (FORTRAN, C, C++, Java, Python and Perl); import from SBML, CellML, and BioPAX; and, export to SVG and HTML. Cell Illustrator employs an extension of hybrid Petri net in an object-oriented style so that biopathway models can include objects such as DNA sequence, molecular density, 3D localization information, transcription with frame-shift, translation with codon table, as well as biochemical reactions.

Natural product-inspired cascade synthesis yields modulators of centrosome integrity.

PubMed

Dückert, Heiko; Pries, Verena; Khedkar, Vivek; Menninger, Sascha; Bruss, Hanna; Bird, Alexander W; Maliga, Zoltan; Brockmeyer, Andreas; Janning, Petra; Hyman, Anthony; Grimme, Stefan; Schürmann, Markus; Preut, Hans; Hübel, Katja; Ziegler, Slava; Kumar, Kamal; Waldmann, Herbert

2011-12-25

In biology-oriented synthesis, the scaffolds of biologically relevant compound classes inspire the synthesis of focused compound collections enriched in bioactivity. This criterion is, in particular, met by the scaffolds of natural products selected in evolution. The synthesis of natural product-inspired compound collections calls for efficient reaction sequences that preferably combine multiple individual transformations in one operation. Here we report the development of a one-pot, twelve-step cascade reaction sequence that includes nine different reactions and two opposing kinds of organocatalysis. The cascade sequence proceeds within 10-30 min and transforms readily available substrates into complex indoloquinolizines that resemble the core tetracyclic scaffold of numerous polycyclic indole alkaloids. Biological investigation of a corresponding focused compound collection revealed modulators of centrosome integrity, termed centrocountins, which caused fragmented and supernumerary centrosomes, chromosome congression defects, multipolar mitotic spindles, acentrosomal spindle poles and multipolar cell division by targeting the centrosome-associated proteins nucleophosmin and Crm1.

Cell Illustrator 4.0: a computational platform for systems biology.

PubMed

Nagasaki, Masao; Saito, Ayumu; Jeong, Euna; Li, Chen; Kojima, Kaname; Ikeda, Emi; Miyano, Satoru

2010-01-01

Cell Illustrator is a software platform for Systems Biology that uses the concept of Petri net for modeling and simulating biopathways. It is intended for biological scientists working at bench. The latest version of Cell Illustrator 4.0 uses Java Web Start technology and is enhanced with new capabilities, including: automatic graph grid layout algorithms using ontology information; tools using Cell System Markup Language (CSML) 3.0 and Cell System Ontology 3.0; parameter search module; high-performance simulation module; CSML database management system; conversion from CSML model to programming languages (FORTRAN, C, C++, Java, Python and Perl); import from SBML, CellML, and BioPAX; and, export to SVG and HTML. Cell Illustrator employs an extension of hybrid Petri net in an object-oriented style so that biopathway models can include objects such as DNA sequence, molecular density, 3D localization information, transcription with frame-shift, translation with codon table, as well as biochemical reactions.

Nanomaterials modulate stem cell differentiation: biological interaction and underlying mechanisms.

PubMed

Wei, Min; Li, Song; Le, Weidong

2017-10-25

Stem cells are unspecialized cells that have the potential for self-renewal and differentiation into more specialized cell types. The chemical and physical properties of surrounding microenvironment contribute to the growth and differentiation of stem cells and consequently play crucial roles in the regulation of stem cells' fate. Nanomaterials hold great promise in biological and biomedical fields owing to their unique properties, such as controllable particle size, facile synthesis, large surface-to-volume ratio, tunable surface chemistry, and biocompatibility. Over the recent years, accumulating evidence has shown that nanomaterials can facilitate stem cell proliferation and differentiation, and great effort is undertaken to explore their possible modulating manners and mechanisms on stem cell differentiation. In present review, we summarize recent progress in the regulating potential of various nanomaterials on stem cell differentiation and discuss the possible cell uptake, biological interaction and underlying mechanisms.

A story told by a single nanoparticle in the body fluid: demonstration of dissolution-reprecipitation of nanocrystals in a biological system.

PubMed

Wu, Cheng-Yeu; Young, David; Martel, Jan; Young, John D

2015-01-01

Analysis of the chemical composition of mineral particles found in the body is critical to understand the formation and effects of these entities in vivo. Yet, the possibility that biological fluids may modulate particle composition over time has not been examined. Materials & methods: Mineralo-organic nanoparticles similar to the ones that spontaneously form in human tissues were analyzed using electron microscopy, spectroscopy and proteomic analyses.   We show that the mineralo-organic nanoparticles assimilate various ions and minerals during incubation in ionic solutions simulating body fluids. The particles undergo dissolution-reprecipitation reactions that affect the final protein composition of the particles. The reactions occurring at the mineral-water interface therefore modulate the ionic and organic composition of mineral nanoparticles formed in biological fluids, producing changes that may alter the effects of mineral particles and stones in vivo.

Active module identification in intracellular networks using a memetic algorithm with a new binary decoding scheme.

PubMed

Li, Dong; Pan, Zhisong; Hu, Guyu; Zhu, Zexuan; He, Shan

2017-03-14

Active modules are connected regions in biological network which show significant changes in expression over particular conditions. The identification of such modules is important since it may reveal the regulatory and signaling mechanisms that associate with a given cellular response. In this paper, we propose a novel active module identification algorithm based on a memetic algorithm. We propose a novel encoding/decoding scheme to ensure the connectedness of the identified active modules. Based on the scheme, we also design and incorporate a local search operator into the memetic algorithm to improve its performance. The effectiveness of proposed algorithm is validated on both small and large protein interaction networks.

Purification of complex samples: Implementation of a modular and reconfigurable droplet-based microfluidic platform with cascaded deterministic lateral displacement separation modules

PubMed Central

Pudda, Catherine; Boizot, François; Verplanck, Nicolas; Revol-Cavalier, Frédéric; Berthier, Jean; Thuaire, Aurélie

2018-01-01

Particle separation in microfluidic devices is a common problematic for sample preparation in biology. Deterministic lateral displacement (DLD) is efficiently implemented as a size-based fractionation technique to separate two populations of particles around a specific size. However, real biological samples contain components of many different sizes and a single DLD separation step is not sufficient to purify these complex samples. When connecting several DLD modules in series, pressure balancing at the DLD outlets of each step becomes critical to ensure an optimal separation efficiency. A generic microfluidic platform is presented in this paper to optimize pressure balancing, when DLD separation is connected either to another DLD module or to a different microfluidic function. This is made possible by generating droplets at T-junctions connected to the DLD outlets. Droplets act as pressure controllers, which perform at the same time the encapsulation of DLD sorted particles and the balance of output pressures. The optimized pressures to apply on DLD modules and on T-junctions are determined by a general model that ensures the equilibrium of the entire platform. The proposed separation platform is completely modular and reconfigurable since the same predictive model applies to any cascaded DLD modules of the droplet-based cartridge. PMID:29768490

Apollo 12 crewmen participate in water egress training

NASA Technical Reports Server (NTRS)

1969-01-01

The three prime crewmen of the Apollo 12 lunar landing mission participate in water egress training in the Gulf of Mexico. They have just egressed the Apollo Command Module trainer. The man standing at left is a Manned Spacecraft Center (MSC) swimmer. The crewmen await life raft for helicopter pickup. All four persons are wearing biological isoloation garments. Participating in the training exercise were Astronauts Charles Conrad Jr., commander; Richard F. Gordon Jr., command module pilot; and Alan L. Bean, lunar module pilot.

A preliminary investigation of the Environmental Control and Life Support Subsystem (EC/LSS) for the space construction base manufacturing modules

NASA Technical Reports Server (NTRS)

Wells, H. B.

1977-01-01

The preliminary data of the environmental control and life support subsystem for a space construction base manufacturing module was reported. A space processing module, which is capable of performing production biological experiments, was chosen as a baseline configuration. The primary assemblies and components considered for use were humidity and temperature control, ventilation fan, cabin fan, water separator, condensate storage, overboard dumping, distribution system, contaminant monitoring, cabin sensors, and fire and smoke detection.

Full load of ESA experiments on Maxus-2 sounding rocket

NASA Astrophysics Data System (ADS)

1995-11-01

Maxus sounding rockets are built and commercialised by an industrial joint venture, a team comprising of the Swedish Space Corporation (SSC) and DASA of Germany. ESA is fully funding the scientific payload for this mission. The payload comprises 8 experiments spanning the fields of fluid physics, electrophoresis and cell biology. Scientists from Belgium, France, Germany and Switzerland designed these experiments and the hardware was built by Swedish, German and Italian firms. The experiments are accommodated in 5 autonomous experiment modules and account for an overall mass of about 500 kg out of a total payload of about 800 kg. The first module contains an experiment which aims to check the static and dynamic behaviour of liquids at corners and edges. The second contains a biological experiment on two unicellular organisms (loxodes and paramecium). In their natural habitat (lakes), these organisms make use of the gravity vector for their orientation. Their swimming behaviour in microgravity will be observed on Earth in real time. The third module houses two other biology experiments. One examines the effect of microgravity on particle ingestion of gold beads by human macrophage cells (a type of white blood cell). Macrophage cells digest foreign particles, such as bacteria and viruses, thereby performing an important function in our immune system. The other experiment investigates the influence of weightlessness on the structure of lymphocytes (white blood cells). The fourth module accommodates three different experiments all dealing with convection phenomena due to surface-tension instabilities (Marangoni convection). Surface tension is that property of liquids which makes raindrops nearly spherical and allows insects to move on water surfaces. These phenomena, which are masked by the effect of gravity on Earth, can be easily studied in microgravity conditions. The fifth module contains an experiment that deals with electrophoresis, i.e. a process which is used to separate biological products in solution by application of a strong electric field. A highly concentrated solution with two proteins will be separated into its fractions and collected in a set of 59 syringes.

Land Application of Wastes: An Educational Program. Soil as a Treatment Medium - Module 3, Objectives, Script and Booklet.

ERIC Educational Resources Information Center

Clarkson, W. W.; And Others

This module examines the basic properties of soil which have an influence on the success of land treatment of wastes. These relevant properties include soil texture, soil structure, permeability, infiltration, available water capacity, and cation exchange capacity. Biological, chemical and physical mechanisms work to remove and renovate wastes…

Efficacy of Multimedia Learning Modules as Preparation for Lecture-Based Tutorials in Electromagnetism

ERIC Educational Resources Information Center

Moore, James Christopher

2018-01-01

We have investigated the efficacy of on-line, multimedia learning modules (MLMs) as preparation for in-class, lecture-based tutorials in electromagnetism in a physics course for natural science majors (biology and marine science). Specifically, we report the results of a multiple-group pre/post-test research design comparing two groups receiving…

Thermodynamics of Irreversible Processes. Physical Processes in Terrestrial and Aquatic Ecosystems, Transport Processes.

ERIC Educational Resources Information Center

Levin, Michael; Gallucci, V. F.

These materials were designed to be used by life science students for instruction in the application of physical theory to ecosystem operation. Most modules contain computer programs which are built around a particular application of a physical process. This module describes the application of irreversible thermodynamics to biology. It begins with…

Molecular locks and keys: the role of small molecules in phytohormone research

PubMed Central

Fonseca, Sandra; Rosado, Abel; Vaughan-Hirsch, John; Bishopp, Anthony; Chini, Andrea

2014-01-01

Plant adaptation, growth and development rely on the integration of many environmental and endogenous signals that collectively determine the overall plant phenotypic plasticity. Plant signaling molecules, also known as phytohormones, are fundamental to this process. These molecules act at low concentrations and regulate multiple aspects of plant fitness and development via complex signaling networks. By its nature, phytohormone research lies at the interface between chemistry and biology. Classically, the scientific community has always used synthetic phytohormones and analogs to study hormone functions and responses. However, recent advances in synthetic and combinational chemistry, have allowed a new field, plant chemical biology, to emerge and this has provided a powerful tool with which to study phytohormone function. Plant chemical biology is helping to address some of the most enduring questions in phytohormone research such as: Are there still undiscovered plant hormones? How can we identify novel signaling molecules? How can plants activate specific hormone responses in a tissue-specific manner? How can we modulate hormone responses in one developmental context without inducing detrimental effects on other processes? The chemical genomics approaches rely on the identification of small molecules modulating different biological processes and have recently identified active forms of plant hormones and molecules regulating many aspects of hormone synthesis, transport and response. We envision that the field of chemical genomics will continue to provide novel molecules able to elucidate specific aspects of hormone-mediated mechanisms. In addition, compounds blocking specific responses could uncover how complex biological responses are regulated. As we gain information about such compounds we can design small alterations to the chemical structure to further alter specificity, enhance affinity or modulate the activity of these compounds. PMID:25566283

A novel filter bank for biotelemetry.

PubMed

Karagözoglu, B

2001-03-01

In a multichannel biotelemetry system, signals taken from a patient are distributed along the available frequency range (bandwidth) of the system through frequency-division-multiplexing, and combined into a single composite signal. Biological signals that are limited to low frequencies (below 10 Hz) modulate the frequencies of respective sub-carriers. Other biological signals are carried in amplitude-modulated forms. It is recognized that recovering original signals from a composite signal at the receiver side is a technical challenge when a telemetry system with narrow bandwidth capacity is used, since such a system leaves little frequency spacing between information channels. A filter bank is therefore utilized for recovering biological signals that are transmitted. The filter bank contains filter units comprising switched-capacitor filter integrated circuits. The filters have two distinct and opposing outputs (band-stop (notch) and band-pass). Since most biological signals are at low frequencies, and modulated signals occupy a narrow band around the carrier, notch filters can be used to efficiently stop signals in the narrow frequency range. Once the interim channels are removed, other channels become well separated from each other, and band-pass filters can select them. In the proposed system, efficient filtering of closely packed channels is achieved, with low interference, from neighboring channels. The filter bank is applied to a system that carries four biological signals and a battery status indicator signal. Experimental results reinforce theoretical predictions that the filter bank successfully de-multiplexes closely packed information channels with low crosstalk between them. It is concluded that the proposed filter bank allows utilization of cost-effective multichannel biotelemetry systems that are designed around commercial audio devices, and that it can be readily adapted to a broad range of physiological recording requirements.

Graphic Biology Laboratory Modules for the Blind.

ERIC Educational Resources Information Center

Brooks, Austin E.

The goal of this project was to devise new methods of producing tactile facsimiles of microscopic images for the blind and visually impaired biology students at the secondary and college level. The numerous raised-line images that were produced were assembled along with brailled and large print student instructions, audio cassette tapes describing…

Efficacy of a Meiosis Learning Module Developed for the Virtual Cell Animation Collection

ERIC Educational Resources Information Center

Goff, Eric E.; Reindl, Katie M.; Johnson, Christina; McClean, Phillip; Offerdahl, Erika G.; Schroeder, Noah L.; White, Alan R.

2017-01-01

Recent reports calling for change in undergraduate biology education have resulted in the redesign of many introductory biology courses. Reports on one common change to course structure, the active-learning environment, have placed an emphasis on student preparation, noting that the positive outcomes of active learning in the classroom depend…

Exploring Cystic Fibrosis Using Bioinformatics Tools: A Module Designed for the Freshman Biology Course

ERIC Educational Resources Information Center

Zhang, Xiaorong

2011-01-01

We incorporated a bioinformatics component into the freshman biology course that allows students to explore cystic fibrosis (CF), a common genetic disorder, using bioinformatics tools and skills. Students learn about CF through searching genetic databases, analyzing genetic sequences, and observing the three-dimensional structures of proteins…

Preliminary Investigation of the Role of Cellular Immunity in Estrous Cycle Modulation of Post-Resection Breast Cancer Spread

DTIC Science & Technology

2004-08-01

established MTCIL tumor rolls retain this unique biologic feature. -ll suspeniionsw from sth moat vsital porn MTP ntutur arnd injected we inoutlated...rather than linear or continuous process. This biologic growth pattern is not unique nor unprecedented. Growth studies in children using serial height

An improved method to quantitate mature plant microRNA in biological matrices using periodate treatment and internal control

USDA-ARS?s Scientific Manuscript database

MicroRNAs (miRNAs) ubiquitously exist in microorganisms, plants and animals, and appear to modulate a wide range of critical biological processes. However, no definitive conclusion has been reached regarding the uptake of exogenous dietary small RNAs into mammalian circulation and organs and cross-k...

Crystallography of biological fluid as a method for evaluating its physicochemical characteristics.

PubMed

Martusevich, A K; Kamakin, N F

2007-03-01

Using an integral qualitative and quantitative approach to the studies of initiation of the biological material crystallogenesis, we showed in experiments with normal human saliva that the external characteristics of biological fluid (pH, osmolality, and environmental temperature) determine the results of crystallization (tesigraphic facies). The main external (macroenvironment) and inner (microenvironment) factors of biological fluid crystal formation, determining specific features of the tesigraphic facies, were distinguished and classified. The informative value of differential analysis of biomaterial properties by means of modulating the environmental conditions is established.

Network-Based Disease Module Discovery by a Novel Seed Connector Algorithm with Pathobiological Implications.

PubMed

Wang, Rui-Sheng; Loscalzo, Joseph

2018-05-20

Understanding the genetic basis of complex diseases is challenging. Prior work shows that disease-related proteins do not typically function in isolation. Rather, they often interact with each other to form a network module that underlies dysfunctional mechanistic pathways. Identifying such disease modules will provide insights into a systems-level understanding of molecular mechanisms of diseases. Owing to the incompleteness of our knowledge of disease proteins and limited information on the biological mediators of pathobiological processes, the key proteins (seed proteins) for many diseases appear scattered over the human protein-protein interactome and form a few small branches, rather than coherent network modules. In this paper, we develop a network-based algorithm, called the Seed Connector algorithm (SCA), to pinpoint disease modules by adding as few additional linking proteins (seed connectors) to the seed protein pool as possible. Such seed connectors are hidden disease module elements that are critical for interpreting the functional context of disease proteins. The SCA aims to connect seed disease proteins so that disease mechanisms and pathways can be decoded based on predicted coherent network modules. We validate the algorithm using a large corpus of 70 complex diseases and binding targets of over 200 drugs, and demonstrate the biological relevance of the seed connectors. Lastly, as a specific proof of concept, we apply the SCA to a set of seed proteins for coronary artery disease derived from a meta-analysis of large-scale genome-wide association studies and obtain a coronary artery disease module enriched with important disease-related signaling pathways and drug targets not previously recognized. Copyright © 2018 Elsevier Ltd. All rights reserved.

Analyzing the genes related to Alzheimer's disease via a network and pathway-based approach.

PubMed

Hu, Yan-Shi; Xin, Juncai; Hu, Ying; Zhang, Lei; Wang, Ju

2017-04-27

Our understanding of the molecular mechanisms underlying Alzheimer's disease (AD) remains incomplete. Previous studies have revealed that genetic factors provide a significant contribution to the pathogenesis and development of AD. In the past years, numerous genes implicated in this disease have been identified via genetic association studies on candidate genes or at the genome-wide level. However, in many cases, the roles of these genes and their interactions in AD are still unclear. A comprehensive and systematic analysis focusing on the biological function and interactions of these genes in the context of AD will therefore provide valuable insights to understand the molecular features of the disease. In this study, we collected genes potentially associated with AD by screening publications on genetic association studies deposited in PubMed. The major biological themes linked with these genes were then revealed by function and biochemical pathway enrichment analysis, and the relation between the pathways was explored by pathway crosstalk analysis. Furthermore, the network features of these AD-related genes were analyzed in the context of human interactome and an AD-specific network was inferred using the Steiner minimal tree algorithm. We compiled 430 human genes reported to be associated with AD from 823 publications. Biological theme analysis indicated that the biological processes and biochemical pathways related to neurodevelopment, metabolism, cell growth and/or survival, and immunology were enriched in these genes. Pathway crosstalk analysis then revealed that the significantly enriched pathways could be grouped into three interlinked modules-neuronal and metabolic module, cell growth/survival and neuroendocrine pathway module, and immune response-related module-indicating an AD-specific immune-endocrine-neuronal regulatory network. Furthermore, an AD-specific protein network was inferred and novel genes potentially associated with AD were identified. By means of network and pathway-based methodology, we explored the pathogenetic mechanism underlying AD at a systems biology level. Results from our work could provide valuable clues for understanding the molecular mechanism underlying AD. In addition, the framework proposed in this study could be used to investigate the pathological molecular network and genes relevant to other complex diseases or phenotypes.

From systems biology to dynamical neuropharmacology: proposal for a new methodology.

PubMed

Erdi, P; Kiss, T; Tóth, J; Ujfalussy, B; Zalányi, L

2006-07-01

The concepts and methods of systems biology are extended to neuropharmacology in order to test and design drugs for the treatment of neurological and psychiatric disorders. Computational modelling by integrating compartmental neural modelling techniques and detailed kinetic descriptions of pharmacological modulation of transmitter-receptor interaction is offered as a method to test the electrophysiological and behavioural effects of putative drugs. Even more, an inverse method is suggested as a method for controlling a neural system to realise a prescribed temporal pattern. In particular, as an application of the proposed new methodology, a computational platform is offered to analyse the generation and pharmacological modulation of theta rhythm related to anxiety.

BioSIGHT: Interactive Visualization Modules for Science Education

NASA Technical Reports Server (NTRS)

Wong, Wee Ling

1998-01-01

Redefining science education to harness emerging integrated media technologies with innovative pedagogical goals represents a unique challenge. The Integrated Media Systems Center (IMSC) is the only engineering research center in the area of multimedia and creative technologies sponsored by the National Science Foundation. The research program at IMSC is focused on developing advanced technologies that address human-computer interfaces, database management, and high-speed network capabilities. The BioSIGHT project at is a demonstration technology project in the area of education that seeks to address how such emerging multimedia technologies can make an impact on science education. The scope of this project will help solidify NASA's commitment for the development of innovative educational resources that promotes science literacy for our students and the general population as well. These issues must be addressed as NASA marches toward the goal of enabling human space exploration that requires an understanding of life sciences in space. The IMSC BioSIGHT lab was established with the purpose of developing a novel methodology that will map a high school biology curriculum into a series of interactive visualization modules that can be easily incorporated into a space biology curriculum. Fundamental concepts in general biology must be mastered in order to allow a better understanding and application for space biology. Interactive visualization is a powerful component that can capture the students' imagination, facilitate their assimilation of complex ideas, and help them develop integrated views of biology. These modules will augment the role of the teacher and will establish the value of student-centered interactivity, both in an individual setting as well as in a collaborative learning environment. Students will be able to interact with the content material, explore new challenges, and perform virtual laboratory simulations. The BioSIGHT effort is truly cross-disciplinary in nature and requires expertise from many areas including Biology, Computer Science Electrical Engineering, Education, and the Cognitive Sciences. The BioSIGHT team includes a scientific illustrator, educational software designer, computer programmers as well as IMSC graduate and undergraduate students.

Network module detection: Affinity search technique with the multi-node topological overlap measure

PubMed Central

Li, Ai; Horvath, Steve

2009-01-01

Background Many clustering procedures only allow the user to input a pairwise dissimilarity or distance measure between objects. We propose a clustering method that can input a multi-point dissimilarity measure d(i1, i2, ..., iP) where the number of points P can be larger than 2. The work is motivated by gene network analysis where clusters correspond to modules of highly interconnected nodes. Here, we define modules as clusters of network nodes with high multi-node topological overlap. The topological overlap measure is a robust measure of interconnectedness which is based on shared network neighbors. In previous work, we have shown that the multi-node topological overlap measure yields biologically meaningful results when used as input of network neighborhood analysis. Findings We adapt network neighborhood analysis for the use of module detection. We propose the Module Affinity Search Technique (MAST), which is a generalized version of the Cluster Affinity Search Technique (CAST). MAST can accommodate a multi-node dissimilarity measure. Clusters grow around user-defined or automatically chosen seeds (e.g. hub nodes). We propose both local and global cluster growth stopping rules. We use several simulations and a gene co-expression network application to argue that the MAST approach leads to biologically meaningful results. We compare MAST with hierarchical clustering and partitioning around medoid clustering. Conclusion Our flexible module detection method is implemented in the MTOM software which can be downloaded from the following webpage: PMID:19619323

MINE: Module Identification in Networks

PubMed Central

2011-01-01

Background Graphical models of network associations are useful for both visualizing and integrating multiple types of association data. Identifying modules, or groups of functionally related gene products, is an important challenge in analyzing biological networks. However, existing tools to identify modules are insufficient when applied to dense networks of experimentally derived interaction data. To address this problem, we have developed an agglomerative clustering method that is able to identify highly modular sets of gene products within highly interconnected molecular interaction networks. Results MINE outperforms MCODE, CFinder, NEMO, SPICi, and MCL in identifying non-exclusive, high modularity clusters when applied to the C. elegans protein-protein interaction network. The algorithm generally achieves superior geometric accuracy and modularity for annotated functional categories. In comparison with the most closely related algorithm, MCODE, the top clusters identified by MINE are consistently of higher density and MINE is less likely to designate overlapping modules as a single unit. MINE offers a high level of granularity with a small number of adjustable parameters, enabling users to fine-tune cluster results for input networks with differing topological properties. Conclusions MINE was created in response to the challenge of discovering high quality modules of gene products within highly interconnected biological networks. The algorithm allows a high degree of flexibility and user-customisation of results with few adjustable parameters. MINE outperforms several popular clustering algorithms in identifying modules with high modularity and obtains good overall recall and precision of functional annotations in protein-protein interaction networks from both S. cerevisiae and C. elegans. PMID:21605434

Network module detection: Affinity search technique with the multi-node topological overlap measure.

PubMed

Li, Ai; Horvath, Steve

2009-07-20

Many clustering procedures only allow the user to input a pairwise dissimilarity or distance measure between objects. We propose a clustering method that can input a multi-point dissimilarity measure d(i1, i2, ..., iP) where the number of points P can be larger than 2. The work is motivated by gene network analysis where clusters correspond to modules of highly interconnected nodes. Here, we define modules as clusters of network nodes with high multi-node topological overlap. The topological overlap measure is a robust measure of interconnectedness which is based on shared network neighbors. In previous work, we have shown that the multi-node topological overlap measure yields biologically meaningful results when used as input of network neighborhood analysis. We adapt network neighborhood analysis for the use of module detection. We propose the Module Affinity Search Technique (MAST), which is a generalized version of the Cluster Affinity Search Technique (CAST). MAST can accommodate a multi-node dissimilarity measure. Clusters grow around user-defined or automatically chosen seeds (e.g. hub nodes). We propose both local and global cluster growth stopping rules. We use several simulations and a gene co-expression network application to argue that the MAST approach leads to biologically meaningful results. We compare MAST with hierarchical clustering and partitioning around medoid clustering. Our flexible module detection method is implemented in the MTOM software which can be downloaded from the following webpage: http://www.genetics.ucla.edu/labs/horvath/MTOM/

Detecting phenotype-driven transitions in regulatory network structure.

PubMed

Padi, Megha; Quackenbush, John

2018-01-01

Complex traits and diseases like human height or cancer are often not caused by a single mutation or genetic variant, but instead arise from functional changes in the underlying molecular network. Biological networks are known to be highly modular and contain dense "communities" of genes that carry out cellular processes, but these structures change between tissues, during development, and in disease. While many methods exist for inferring networks and analyzing their topologies separately, there is a lack of robust methods for quantifying differences in network structure. Here, we describe ALPACA (ALtered Partitions Across Community Architectures), a method for comparing two genome-scale networks derived from different phenotypic states to identify condition-specific modules. In simulations, ALPACA leads to more nuanced, sensitive, and robust module discovery than currently available network comparison methods. As an application, we use ALPACA to compare transcriptional networks in three contexts: angiogenic and non-angiogenic subtypes of ovarian cancer, human fibroblasts expressing transforming viral oncogenes, and sexual dimorphism in human breast tissue. In each case, ALPACA identifies modules enriched for processes relevant to the phenotype. For example, modules specific to angiogenic ovarian tumors are enriched for genes associated with blood vessel development, and modules found in female breast tissue are enriched for genes involved in estrogen receptor and ERK signaling. The functional relevance of these new modules suggests that not only can ALPACA identify structural changes in complex networks, but also that these changes may be relevant for characterizing biological phenotypes.

Introducing Mammalian Cell Culture and Cell Viability Techniques in the Undergraduate Biology Laboratory.

PubMed

Bowey-Dellinger, Kristen; Dixon, Luke; Ackerman, Kristin; Vigueira, Cynthia; Suh, Yewseok K; Lyda, Todd; Sapp, Kelli; Grider, Michael; Crater, Dinene; Russell, Travis; Elias, Michael; Coffield, V McNeil; Segarra, Verónica A

2017-01-01

Undergraduate students learn about mammalian cell culture applications in introductory biology courses. However, laboratory modules are rarely designed to provide hands-on experience with mammalian cells or teach cell culture techniques, such as trypsinization and cell counting. Students are more likely to learn about cell culture using bacteria or yeast, as they are typically easier to grow, culture, and manipulate given the equipment, tools, and environment of most undergraduate biology laboratories. In contrast, the utilization of mammalian cells requires a dedicated biological safety cabinet and rigorous antiseptic techniques. For this reason, we have devised a laboratory module and method herein that familiarizes students with common cell culture procedures, without the use of a sterile hood or large cell culture facility. Students design and perform a time-efficient inquiry-based cell viability experiment using HeLa cells and tools that are readily available in an undergraduate biology laboratory. Students will become familiar with common techniques such as trypsinizing cells, cell counting with a hemocytometer, performing serial dilutions, and determining cell viability using trypan blue dye. Additionally, students will work with graphing software to analyze their data and think critically about the mechanism of death on a cellular level. Two different adaptations of this inquiry-based lab are presented-one for non-biology majors and one for biology majors. Overall, these laboratories aim to expose students to mammalian cell culture and basic techniques and help them to conceptualize their application in scientific research.

Introducing Mammalian Cell Culture and Cell Viability Techniques in the Undergraduate Biology Laboratory †

PubMed Central

Bowey-Dellinger, Kristen; Dixon, Luke; Ackerman, Kristin; Vigueira, Cynthia; Suh, Yewseok K.; Lyda, Todd; Sapp, Kelli; Grider, Michael; Crater, Dinene; Russell, Travis; Elias, Michael; Coffield, V. McNeil; Segarra, Verónica A.

2017-01-01

Undergraduate students learn about mammalian cell culture applications in introductory biology courses. However, laboratory modules are rarely designed to provide hands-on experience with mammalian cells or teach cell culture techniques, such as trypsinization and cell counting. Students are more likely to learn about cell culture using bacteria or yeast, as they are typically easier to grow, culture, and manipulate given the equipment, tools, and environment of most undergraduate biology laboratories. In contrast, the utilization of mammalian cells requires a dedicated biological safety cabinet and rigorous antiseptic techniques. For this reason, we have devised a laboratory module and method herein that familiarizes students with common cell culture procedures, without the use of a sterile hood or large cell culture facility. Students design and perform a time-efficient inquiry-based cell viability experiment using HeLa cells and tools that are readily available in an undergraduate biology laboratory. Students will become familiar with common techniques such as trypsinizing cells, cell counting with a hemocytometer, performing serial dilutions, and determining cell viability using trypan blue dye. Additionally, students will work with graphing software to analyze their data and think critically about the mechanism of death on a cellular level. Two different adaptations of this inquiry-based lab are presented—one for non-biology majors and one for biology majors. Overall, these laboratories aim to expose students to mammalian cell culture and basic techniques and help them to conceptualize their application in scientific research. PMID:28861134

A hybrid approach of gene sets and single genes for the prediction of survival risks with gene expression data.

PubMed

Seok, Junhee; Davis, Ronald W; Xiao, Wenzhong

2015-01-01

Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn't been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge.

A Hybrid Approach of Gene Sets and Single Genes for the Prediction of Survival Risks with Gene Expression Data

PubMed Central

Seok, Junhee; Davis, Ronald W.; Xiao, Wenzhong

2015-01-01

Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn’t been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge. PMID:25933378

Life on rock. Scaling down biological weathering in a new experimental design at Biosphere-2

NASA Astrophysics Data System (ADS)

Zaharescu, D. G.; Dontsova, K.; Burghelea, C. I.; Chorover, J.; Maier, R.; Perdrial, J. N.

2012-12-01

Biological colonization and weathering of bedrock on Earth is a major driver of landscape and ecosystem development, its effects reaching out into other major systems such climate and geochemical cycles of elements. In order to understand how microbe-plant-mycorrhizae communities interact with bedrock in the first phases of mineral weathering we developed a novel experimental design in the Desert Biome at Biosphere-2, University of Arizona (U.S.A). This presentation will focus on the development of the experimental setup. Briefly, six enclosed modules were designed to hold 288 experimental columns that will accommodate 4 rock types and 6 biological treatments. Each module is developed on 3 levels. A lower volume, able to withstand the weight of both, rock material and the rest of the structure, accommodates the sampling elements. A middle volume, houses the experimental columns in a dark chamber. A clear, upper section forms the habitat exposed to sunlight. This volume is completely sealed form exterior and it allows a complete control of its air and water parameters. All modules are connected in parallel with a double air purification system that delivers a permanent air flow. This setup is expected to provide a model experiment, able to test important processes in the interaction rock-life at grain-to- molecular scale.

Chemical genomics in plant biology.

PubMed

Sadhukhan, Ayan; Sahoo, Lingaraj; Panda, Sanjib Kumar

2012-06-01

Chemical genomics is a newly emerged and rapidly progressing field in biology, where small chemical molecules bind specifically and reversibly to protein(s) to modulate their function(s), leading to the delineation and subsequent unravelling of biological processes. This approach overcomes problems like lethality and redundancy of classical genetics. Armed with the powerful techniques of combinatorial synthesis, high-throughput screening and target discovery chemical genomics expands its scope to diverse areas in biology. The well-established genetic system of Arabidopsis model allows chemical genomics to enter into the realm of plant biology exploring signaling pathways of growth regulators, endomembrane signaling cascades, plant defense mechanisms and many more events.

Hands-On! Living in the Biosphere: Production, Pattern, Population, and Diversity. Developing Active Learning Module on the Human Dimensions of Global Change.

ERIC Educational Resources Information Center

Brown, Dwight

Biogeography examines questions of organism inventory and pattern, organisms' interactions with the environment, and the processes that create and change inventory, pattern, and interactions. This learning module uses time series maps and simple simulation models to illustrate how human actions alter biological productivity patterns at local and…

GoldenBraid: An Iterative Cloning System for Standardized Assembly of Reusable Genetic Modules

PubMed Central

Sarrion-Perdigones, Alejandro; Falconi, Erica Elvira; Zandalinas, Sara I.; Juárez, Paloma; Fernández-del-Carmen, Asun; Granell, Antonio; Orzaez, Diego

2011-01-01

Synthetic Biology requires efficient and versatile DNA assembly systems to facilitate the building of new genetic modules/pathways from basic DNA parts in a standardized way. Here we present GoldenBraid (GB), a standardized assembly system based on type IIS restriction enzymes that allows the indefinite growth of reusable gene modules made of standardized DNA pieces. The GB system consists of a set of four destination plasmids (pDGBs) designed to incorporate multipartite assemblies made of standard DNA parts and to combine them binarily to build increasingly complex multigene constructs. The relative position of type IIS restriction sites inside pDGB vectors introduces a double loop (“braid”) topology in the cloning strategy that allows the indefinite growth of composite parts through the succession of iterative assembling steps, while the overall simplicity of the system is maintained. We propose the use of GoldenBraid as an assembly standard for Plant Synthetic Biology. For this purpose we have GB-adapted a set of binary plasmids for A. tumefaciens-mediated plant transformation. Fast GB-engineering of several multigene T-DNAs, including two alternative modules made of five reusable devices each, and comprising a total of 19 basic parts are also described. PMID:21750718

GoldenBraid: an iterative cloning system for standardized assembly of reusable genetic modules.

PubMed

Sarrion-Perdigones, Alejandro; Falconi, Erica Elvira; Zandalinas, Sara I; Juárez, Paloma; Fernández-del-Carmen, Asun; Granell, Antonio; Orzaez, Diego

2011-01-01

Synthetic Biology requires efficient and versatile DNA assembly systems to facilitate the building of new genetic modules/pathways from basic DNA parts in a standardized way. Here we present GoldenBraid (GB), a standardized assembly system based on type IIS restriction enzymes that allows the indefinite growth of reusable gene modules made of standardized DNA pieces. The GB system consists of a set of four destination plasmids (pDGBs) designed to incorporate multipartite assemblies made of standard DNA parts and to combine them binarily to build increasingly complex multigene constructs. The relative position of type IIS restriction sites inside pDGB vectors introduces a double loop ("braid") topology in the cloning strategy that allows the indefinite growth of composite parts through the succession of iterative assembling steps, while the overall simplicity of the system is maintained. We propose the use of GoldenBraid as an assembly standard for Plant Synthetic Biology. For this purpose we have GB-adapted a set of binary plasmids for A. tumefaciens-mediated plant transformation. Fast GB-engineering of several multigene T-DNAs, including two alternative modules made of five reusable devices each, and comprising a total of 19 basic parts are also described.

The Fluids Integrated Rack and Light Microscopy Module Integrated Capabilities

NASA Technical Reports Server (NTRS)

Motil, Susan M.; Gati, Frank; Snead, John H.; Hill, Myron E.; Griffin, DeVon W.

2003-01-01

The Fluids Integrated Rack (FIR), a facility class payload, and the Light Microscopy Module (LMM), a subrack payload, are scheduled to be launched in 2005. The LMM integrated into the FIR will provide a unique platform for conducting fluids and biological experiments on ISS. The FIR is a modular, multi-user scientific research facility that will fly in the U.S. laboratory module, Destiny, of the International Space Station (ISS). The first payload in the FIR will be the Light Microscopy Module (LMM). The LMM is planned as a remotely controllable, automated, on-orbit microscope subrack facility, allowing flexible scheduling and control of fluids and biology experiments within the FIR. Key diagnostic capabilities for meeting science requirements include video microscopy to observe microscopic phenomena and dynamic interactions, interferometry to make thin film measurements with nanometer resolution, laser tweezers for particle manipulation, confocal microscopy to provide enhanced three-dimensional visualization of structures, and spectrophotometry to measure photonic properties of materials. The LMM also provides experiment sample containment for frangibles and fluids. This paper will provide a description of the current FIR and LMM designs, planned capabilities and key features. In addition a brief description of the initial five experiments planned for LMM/FIR will be provided.

Rational modular design of metabolic network for efficient production of plant polyphenol pinosylvin.

PubMed

Wu, Junjun; Zhang, Xia; Zhu, Yingjie; Tan, Qinyu; He, Jiacheng; Dong, Mingsheng

2017-05-03

Efficient biosynthesis of the plant polyphenol pinosylvin, which has numerous applications in nutraceuticals and pharmaceuticals, is necessary to make biological production economically viable. To this end, an efficient Escherichia coli platform for pinosylvin production was developed via a rational modular design approach. Initially, different candidate pathway enzymes were screened to construct de novo pinosylvin pathway directly from D-glucose. A comparative analysis of pathway intermediate pools identified that this initial construct led to the intermediate cinnamic acid accumulation. The pinosylvin synthetic pathway was then divided into two new modules separated at cinnamic acid. Combinatorial optimization of transcriptional and translational levels of these two modules resulted in a 16-fold increase in pinosylvin titer. To further improve the concentration of the limiting precursor malonyl-CoA, the malonyl-CoA synthesis module based on clustered regularly interspaced short palindromic repeats interference was assembled and optimized with other two modules. The final pinosylvin titer was improved to 281 mg/L, which was the highest pinosylvin titer even directly from D-glucose without any additional precursor supplementation. The rational modular design approach described here could bolster our capabilities in synthetic biology for value-added chemical production.

Accommodating Those Most at Risk. Responding to a Mismatch in Programme Selection Criteria and Foundation Biology Performance

ERIC Educational Resources Information Center

Kirby, Nicola F.; Dempster, Edith R.

2015-01-01

In South Africa, foundation programmes are a well-established alternative access route to tertiary science study for educationally disadvantaged students. Student access to, and performance in, one such foundation programme has been researched by the authors seeking opportunities to improve student retention. The biology module in particular has…

Expression profiling of ascorbic acid-related genes during tomato fruit development and ripening and in response to stress conditions

USDA-ARS?s Scientific Manuscript database

L-Ascorbate (the reduced form of Vitamin C) participates in diverse biological processes including pathogen defense mechanisms, the modulation of plant growth and morphology and also acts as an enzyme cofactor, and redox status indicator. One of its chief biological functions is as an antioxidant. L...

Practice Makes Pretty Good: Assessment of Primary Literature Reading Abilities across Multiple Large-Enrollment Biology Laboratory Courses

ERIC Educational Resources Information Center

Sato, Brian K.; Kadandale, Pavan; He, Wenliang; Murata, Paige M. N.; Latif, Yama; Warschauer, Mark

2014-01-01

Primary literature is essential for scientific communication and is commonly utilized in undergraduate biology education. Despite this, there is often little time spent "training" our students how to critically analyze a paper. To address this, we introduced a primary literature module in multiple upper-division laboratory courses. In…

Using Primary Literature in an Undergraduate Assignment: Demonstrating Connections among Cellular Processes

ERIC Educational Resources Information Center

Yeong, Foong May

2015-01-01

Learning basic cell biology in an essential module can be daunting to second-year undergraduates, given the depth of information that is provided in major molecular and cell biology textbooks. Moreover, lectures on cellular pathways are organised into sections, such that at the end of lectures, students might not see how various processes are…

Problem-Centered Supplemental Instruction in Biology: Influence on Content Recall, Content Understanding, and Problem Solving Ability

ERIC Educational Resources Information Center

Gardner, Joel; Belland, Brian R.

2017-01-01

To address the need for effective, efficient ways to apply active learning in undergraduate biology courses, in this paper, we propose a problem-centered approach that utilizes supplemental web-based instructional materials based on principles of active learning. We compared two supplementary web-based modules using active learning strategies: the…

Desegregating undergraduate mathematics and biology--interdisciplinary instruction with emphasis on ongoing biomedical research.

PubMed

Robeva, Raina

2009-01-01

The remarkable advances in the field of biology in the last decade, specifically in the areas of biochemistry, genetics, genomics, proteomics, and systems biology, have demonstrated how critically important mathematical models and methods are in addressing questions of vital importance for these disciplines. There is little doubt that the need for utilizing and developing mathematical methods for biology research will only grow in the future. The rapidly increasing demand for scientists with appropriate interdisciplinary skills and knowledge, however, is not being reflected in the way undergraduate mathematics and biology courses are structured and taught in most colleges and universities nationwide. While a number of institutions have stepped forward and addressed this need by creating and offering interdisciplinary courses at the juncture of mathematics and biology, there are still many others at which there is little, if any, interdisciplinary interaction between the curricula. This chapter describes an interdisciplinary course and a textbook in mathematical biology developed collaboratively by faculty from Sweet Briar College and the University of Virginia School of Medicine. The course and textbook are designed to provide a bridge between the mathematical and biological sciences at the lower undergraduate level. The course is developed for and is being taught in a liberal arts setting at Sweet Briar College, Virginia, but some of the advanced modules are used in a course at the University of Virginia for advanced undergraduate and beginning graduate students. The individual modules are relatively independent and can be used as stand-alone projects in conventional mathematics and biology courses. Except for the introductory material, the course and textbook topics are based on current biomedical research.

Competency-based reforms of the undergraduate biology curriculum: integrating the physical and biological sciences.

PubMed

Thompson, Katerina V; Chmielewski, Jean; Gaines, Michael S; Hrycyna, Christine A; LaCourse, William R

2013-06-01

The National Experiment in Undergraduate Science Education project funded by the Howard Hughes Medical Institute is a direct response to the Scientific Foundations for Future Physicians report, which urged a shift in premedical student preparation from a narrow list of specific course work to a more flexible curriculum that helps students develop broad scientific competencies. A consortium of four universities is working to create, pilot, and assess modular, competency-based curricular units that require students to use higher-order cognitive skills and reason across traditional disciplinary boundaries. Purdue University; the University of Maryland, Baltimore County; and the University of Miami are each developing modules and case studies that integrate the biological, chemical, physical, and mathematical sciences. The University of Maryland, College Park, is leading the effort to create an introductory physics for life sciences course that is reformed in both content and pedagogy. This course has prerequisites of biology, chemistry, and calculus, allowing students to apply strategies from the physical sciences to solving authentic biological problems. A comprehensive assessment plan is examining students' conceptual knowledge of physics, their attitudes toward interdisciplinary approaches, and the development of specific scientific competencies. Teaching modules developed during this initial phase will be tested on multiple partner campuses in preparation for eventual broad dissemination.

The effect of fasting during Ramadan on parameters of the haematological and steroidal modules of the athletes biological passport - a pilot study.

PubMed

Alsaadi, K; Voss, S C; Kraiem, S; Alwahaibi, A; Alyazedi, S; Dbes, N; Goebel, R; Mohamed-Ali, V; Alsowaidi, S; Seyam, A M; Bashraheel, A S; Alsayrafi, M; Georgakopoulos, C

2015-01-01

This study investigated the effect of Ramadan on the haematological and steroid module of the Athletes Biological Passport (ABP) of the World Anti-Doping Agency (WADA). Nine healthy physically active subjects were tested in the morning and afternoon for two days before and three days during Ramadan. Sample collection and all analyses were performed according to WADA technical documents. Although there were significant changes in the haemoglobin concentration during Ramadan, especially during the first fasting week, none of the subjects in this study exceeded the individually calculated thresholds of the ABP. No significant effects on testosterone/epitestosterone (T/E) ratio were observed but only the afternoon specific gravity (SG) of the urine was elevated. Thus, when urinary steroid concentrations are required, SG corrections need to be performed. The haematological and the steroid module of the ABP can be reliably applied during Ramadan as the observed changes are only marginal. Copyright © 2015 John Wiley & Sons, Ltd.

Dance expertise modulates visual sensitivity to complex biological movements.

PubMed

Orlandi, Andrea; Zani, Alberto; Proverbio, Alice Mado

2017-09-01

Motor resonance processes that occur when observing an individual perform an action may be modulated by acquired visuomotor expertise. We used the event-related potential (EEG/ERP) technique to investigate the ability to automatically recognize a subtle difference between very similar novel contemporary dance movements. Twelve professional dancers and twelve non-dancers were shown 212 pairs of videos of complex whole-body movements that lasted 3s. The second of each pair was the repetition of the previous movement or a slight variation of it (deviance). The participants were engaged in a secondary attentional task. Modulation of a larger centro-parietal N400 effect and a reduction of the Late Positivity amplitude (repetition suppression effect) were identified in response to deviant stimuli only in the dancers. Source reconstruction (swLORETA) showed activations in biological motion, body and face processing related areas, and fronto-parietal and limbic systems. The current findings provide evidence that acquired dance expertise modifies the ability to visually code whole-body complex movements. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuropeptide substance P and the immune response.

PubMed

Mashaghi, Alireza; Marmalidou, Anna; Tehrani, Mohsen; Grace, Peter M; Pothoulakis, Charalabos; Dana, Reza

2016-11-01

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of the activity of immune cells. This review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immunobiology of substance P and discuss the clinical implications of its ability to modulate the immune response.

Electrodermal reactivity and its association to substance use disorders.

PubMed

Taylor, Jeanette

2004-11-01

Poor electrodermal response modulation is associated with substance use disorders, but the specificity of the relationship has not been tested. To test this, 112 college students were assessed for psychiatric symptoms using structured interviews and for ability to modulate skin conductance responses to 2-s 92- or 110-dB white noise blasts that varied in temporal predictability. Twenty-eight good and 28 poor modulators were compared on symptoms of alcohol and illicit drug use disorders, personality disorders (antisocial, borderline, histrionic, and narcissistic), social and specific phobia, and depression. As expected, poor modulators had significantly more symptoms of substance use disorders than good modulators. Groups did not differ in symptoms of anxiety disorder, depression, or personality disorders marked by disinhibition. Poor electrodermal response modulation may reflect a biological risk factor for substance use disorders in particular.

Modules for in vitro metabolic engineering: Pathway assembly for bio-based production of value-added chemicals.

PubMed

Taniguchi, Hironori; Okano, Kenji; Honda, Kohsuke

2017-06-01

Bio-based chemical production has drawn attention regarding the realization of a sustainable society. In vitro metabolic engineering is one of the methods used for the bio-based production of value-added chemicals. This method involves the reconstitution of natural or artificial metabolic pathways by assembling purified/semi-purified enzymes in vitro . Enzymes from distinct sources can be combined to construct desired reaction cascades with fewer biological constraints in one vessel, enabling easier pathway design with high modularity. Multiple modules have been designed, built, tested, and improved by different groups for different purpose. In this review, we focus on these in vitro metabolic engineering modules, especially focusing on the carbon metabolism, and present an overview of input modules, output modules, and other modules related to cofactor management.

Revealing the Hidden Relationship by Sparse Modules in Complex Networks with a Large-Scale Analysis

PubMed Central

Jiao, Qing-Ju; Huang, Yan; Liu, Wei; Wang, Xiao-Fan; Chen, Xiao-Shuang; Shen, Hong-Bin

2013-01-01

One of the remarkable features of networks is module that can provide useful insights into not only network organizations but also functional behaviors between their components. Comprehensive efforts have been devoted to investigating cohesive modules in the past decade. However, it is still not clear whether there are important structural characteristics of the nodes that do not belong to any cohesive module. In order to answer this question, we performed a large-scale analysis on 25 complex networks with different types and scales using our recently developed BTS (bintree seeking) algorithm, which is able to detect both cohesive and sparse modules in the network. Our results reveal that the sparse modules composed by the cohesively isolated nodes widely co-exist with the cohesive modules. Detailed analysis shows that both types of modules provide better characterization for the division of a network into functional units than merely cohesive modules, because the sparse modules possibly re-organize the nodes in the so-called cohesive modules, which lack obvious modular significance, into meaningful groups. Compared with cohesive modules, the sizes of sparse ones are generally smaller. Sparse modules are also found to have preferences in social and biological networks than others. PMID:23762457

Thermoelectric generator having a resiliently mounted removable thermoelectric module

DOEpatents

Purdy, David L.; Shapiro, Zalman M.; Hursen, Thomas F.; Maurer, Gerould W.

1976-11-02

An electrical generator having an Isotopic Heat Capsule including radioactive fuel rod 21 as a primary heat source and Thermoelectric Modules 41 and 43 as converters. The Biological Shield for the Capsule is suspended from Spiders at each end each consisting of pretensioned rods 237 and 239 defining planes at right angles to each other. The Modules are mounted in cups 171 of transition members 173 of a heat rejection Fin Assembly whose fins 195 and 197 extend from both sides of the transition member 173 for effective cooling.

Stimulated Raman scattering microscopy by Nyquist modulation of a two-branch ultrafast fiber source.

PubMed

Riek, Claudius; Kocher, Claudius; Zirak, Peyman; Kölbl, Christoph; Fimpel, Peter; Leitenstorfer, Alfred; Zumbusch, Andreas; Brida, Daniele

2016-08-15

A highly stable setup for stimulated Raman scattering (SRS) microscopy is presented. It is based on a two-branch femtosecond Er:fiber laser operating at a 40 MHz repetition rate. One of the outputs is directly modulated at the Nyquist frequency with an integrated electro-optic modulator (EOM). This compact source combines a jitter-free pulse synchronization with a broad tunability and allows for shot-noise limited SRS detection. The performance of the SRS microscope is illustrated with measurements on samples from material science and cell biology.

Apollo 12 crewmen participate in water egress training

NASA Image and Video Library

1969-09-20

S69-52990 (20 Sept. 1969) --- The three prime crew men of the Apollo 12 lunar landing mission participate in water egress training in the Gulf of Mexico. They have just egressed the Apollo Command Module (CM) trainer. The man standing at left is a Manned Spacecraft Center's (MSC) swimmer. The crew men await in life raft for helicopter pickup. All four persons are wearing biological isolation garments. Participating in the training exercise were astronauts Charles Conrad Jr., commander; Richard F. Gordon Jr., command module pilot; and Alan L. Bean, lunar module pilot.

Gene co-expression network analysis in Rhodobacter capsulatus and application to comparative expression analysis of Rhodobacter sphaeroides

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

Pena-Castillo, Lourdes; Mercer, Ryan; Gurinovich, Anastasia

2014-08-28

The genus Rhodobacter contains purple nonsulfur bacteria found mostly in freshwater environments. Representative strains of two Rhodobacter species, R. capsulatus and R. sphaeroides, have had their genomes fully sequenced and both have been the subject of transcriptional profiling studies. Gene co-expression networks can be used to identify modules of genes with similar expression profiles. Functional analysis of gene modules can then associate co-expressed genes with biological pathways, and network statistics can determine the degree of module preservation in related networks. In this paper, we constructed an R. capsulatus gene co-expression network, performed functional analysis of identified gene modules, and investigatedmore » preservation of these modules in R. capsulatus proteomics data and in R. sphaeroides transcriptomics data. Results: The analysis identified 40 gene co-expression modules in R. capsulatus. Investigation of the module gene contents and expression profiles revealed patterns that were validated based on previous studies supporting the biological relevance of these modules. We identified two R. capsulatus gene modules preserved in the protein abundance data. We also identified several gene modules preserved between both Rhodobacter species, which indicate that these cellular processes are conserved between the species and are candidates for functional information transfer between species. Many gene modules were non-preserved, providing insight into processes that differentiate the two species. In addition, using Local Network Similarity (LNS), a recently proposed metric for expression divergence, we assessed the expression conservation of between-species pairs of orthologs, and within-species gene-protein expression profiles. Conclusions: Our analyses provide new sources of information for functional annotation in R. capsulatus because uncharacterized genes in modules are now connected with groups of genes that constitute a joint functional annotation. We identified R. capsulatus modules enriched with genes for ribosomal proteins, porphyrin and bacteriochlorophyll anabolism, and biosynthesis of secondary metabolites to be preserved in R. sphaeroides whereas modules related to RcGTA production and signalling showed lack of preservation in R. sphaeroides. In addition, we demonstrated that network statistics may also be applied within-species to identify congruence between mRNA expression and protein abundance data for which simple correlation measurements have previously had mixed results.« less

Integration of an optical CMOS sensor with a microfluidic channel allows a sensitive readout for biological assays in point-of-care tests.

PubMed

Van Dorst, Bieke; Brivio, Monica; Van Der Sar, Elfried; Blom, Marko; Reuvekamp, Simon; Tanzi, Simone; Groenhuis, Roelf; Adojutelegan, Adewole; Lous, Erik-Jan; Frederix, Filip; Stuyver, Lieven J

2016-04-15

In this manuscript, a microfluidic detection module, which allows a sensitive readout of biological assays in point-of-care (POC) tests, is presented. The proposed detection module consists of a microfluidic flow cell with an integrated Complementary Metal-Oxide-Semiconductor (CMOS)-based single photon counting optical sensor. Due to the integrated sensor-based readout, the detection module could be implemented as the core technology in stand-alone POC tests, for use in mobile or rural settings. The performance of the detection module was demonstrated in three assays: a peptide, a protein and an antibody detection assay. The antibody detection assay with readout in the detection module proved to be 7-fold more sensitive that the traditional colorimetric plate-based ELISA. The protein and peptide assay showed a lower limit of detection (LLOD) of 200 fM and 460 fM respectively. Results demonstrate that the sensitivity of the immunoassays is comparable with lab-based immunoassays and at least equal or better than current mainstream POC devices. This sensitive readout holds the potential to develop POC tests, which are able to detect low concentrations of biomarkers. This will broaden the diagnostic capabilities at the clinician's office and at patient's home, where currently only the less sensitive lateral flow and dipstick POC tests are implemented. Copyright © 2015 Elsevier B.V. All rights reserved.

miRegulome: a knowledge-base of miRNA regulomics and analysis.

PubMed

Barh, Debmalya; Kamapantula, Bhanu; Jain, Neha; Nalluri, Joseph; Bhattacharya, Antaripa; Juneja, Lucky; Barve, Neha; Tiwari, Sandeep; Miyoshi, Anderson; Azevedo, Vasco; Blum, Kenneth; Kumar, Anil; Silva, Artur; Ghosh, Preetam

2015-08-05

miRNAs regulate post transcriptional gene expression by targeting multiple mRNAs and hence can modulate multiple signalling pathways, biological processes, and patho-physiologies. Therefore, understanding of miRNA regulatory networks is essential in order to modulate the functions of a miRNA. The focus of several existing databases is to provide information on specific aspects of miRNA regulation. However, an integrated resource on the miRNA regulome is currently not available to facilitate the exploration and understanding of miRNA regulomics. miRegulome attempts to bridge this gap. The current version of miRegulome v1.0 provides details on the entire regulatory modules of miRNAs altered in response to chemical treatments and transcription factors, based on validated data manually curated from published literature. Modules of miRegulome (upstream regulators, downstream targets, miRNA regulated pathways, functions, diseases, etc) are hyperlinked to an appropriate external resource and are displayed visually to provide a comprehensive understanding. Four analysis tools are incorporated to identify relationships among different modules based on user specified datasets. miRegulome and its tools are helpful in understanding the biology of miRNAs and will also facilitate the discovery of biomarkers and therapeutics. With added features in upcoming releases, miRegulome will be an essential resource to the scientific community. http://bnet.egr.vcu.edu/miRegulome.

A bioarchitectonic approach to the modular engineering of metabolism.

PubMed

Kerfeld, Cheryl A

2017-09-26

Dissociating the complexity of metabolic processes into modules is a shift in focus from the single gene/gene product to functional and evolutionary units spanning the scale of biological organization. When viewing the levels of biological organization through this conceptual lens, modules are found across the continuum: domains within proteins, co-regulated groups of functionally associated genes, operons, metabolic pathways and (sub)cellular compartments. Combining modules as components or subsystems of a larger system typically leads to increased complexity and the emergence of new functions. By virtue of their potential for 'plug and play' into new contexts, modules can be viewed as units of both evolution and engineering. Through consideration of lessons learned from recent efforts to install new metabolic modules into cells and the emerging understanding of the structure, function and assembly of protein-based organelles, bacterial microcompartments, a structural bioengineering approach is described: one that builds from an architectural vocabulary of protein domains. This bioarchitectonic approach to engineering cellular metabolism can be applied to microbial cell factories, used in the programming of members of synthetic microbial communities or used to attain additional levels of metabolic organization in eukaryotic cells for increasing primary productivity and as the foundation of a green economy.This article is part of the themed issue 'Enhancing photosynthesis in crop plants: targets for improvement'. © 2017 The Author(s).

Simultaneous off-axis multiplexed holography and regular fluorescence microscopy of biological cells.

PubMed

Nygate, Yoav N; Singh, Gyanendra; Barnea, Itay; Shaked, Natan T

2018-06-01

We present a new technique for obtaining simultaneous multimodal quantitative phase and fluorescence microscopy of biological cells, providing both quantitative phase imaging and molecular specificity using a single camera. Our system is based on an interferometric multiplexing module, externally positioned at the exit of an optical microscope. In contrast to previous approaches, the presented technique allows conventional fluorescence imaging, rather than interferometric off-axis fluorescence imaging. We demonstrate the presented technique for imaging fluorescent beads and live biological cells.

[Exploration of common biological pathways for attention deficit hyperactivity disorder and low birth weight].

PubMed

Xiang, Bo; Yu, Minglan; Liang, Xuemei; Lei, Wei; Huang, Chaohua; Chen, Jing; He, Wenying; Zhang, Tao; Li, Tao; Liu, Kezhi

2017-12-10

To explore common biological pathways for attention deficit hyperactivity disorder (ADHD) and low birth weight (LBW). Thei-Gsea4GwasV2 software was used to analyze the result of genome-wide association analysis (GWAS) for LBW (pathways were derived from Reactome), and nominally significant (P< 0.05, FDR< 0.25) pathways were tested for replication in ADHD.Significant pathways were analyzed with DAPPLE and Reatome FI software to identify genes involved in such pathways, with each cluster enriched with the gene ontology (GO). The Centiscape2.0 software was used to calculate the degree of genetic networks and the betweenness value to explore the core node (gene). Weighed gene co-expression network analysis (WGCNA) was then used to explore the co-expression of genes in these pathways.With gene expression data derived from BrainSpan, GO enrichment was carried out for each gene module. Eleven significant biological pathways was identified in association with LBW, among which two (Selenoamino acid metabolism and Diseases associated with glycosaminoglycan metabolism) were replicated during subsequent ADHD analysis. Network analysis of 130 genes in these pathways revealed that some of the sub-networksare related with morphology of cerebellum, development of hippocampus, and plasticity of synaptic structure. Upon co-expression network analysis, 120 genes passed the quality control and were found to express in 3 gene modules. These modules are mainly related to the regulation of synaptic structure and activity regulation. ADHD and LBW share some biological regulation processes. Anomalies of such proces sesmay predispose to ADHD.

Engineering scalable biological systems

PubMed Central

2010-01-01

Synthetic biology is focused on engineering biological organisms to study natural systems and to provide new solutions for pressing medical, industrial and environmental problems. At the core of engineered organisms are synthetic biological circuits that execute the tasks of sensing inputs, processing logic and performing output functions. In the last decade, significant progress has been made in developing basic designs for a wide range of biological circuits in bacteria, yeast and mammalian systems. However, significant challenges in the construction, probing, modulation and debugging of synthetic biological systems must be addressed in order to achieve scalable higher-complexity biological circuits. Furthermore, concomitant efforts to evaluate the safety and biocontainment of engineered organisms and address public and regulatory concerns will be necessary to ensure that technological advances are translated into real-world solutions. PMID:21468204

Bringing Global Climate Change Education to Alabama Middle School and High School Classrooms

NASA Astrophysics Data System (ADS)

Lee, M.; Mitra, C.; Percival, E.; Thomas, A.; Lucy, T.; Hickman, E.; Cox, J.; Chaudhury, S. R.; Rodger, C.

2013-12-01

A NASA-funded Innovations in Climate Education (NICE) Program has been launched in Alabama to improve high school and middle school education in climate change science. The overarching goal is to generate a better informed public that understands the consequences of climate change and can contribute to sound decision making on related issues. Inquiry based NICE modules have been incorporated into the existing course of study for 9-12 grade biology, chemistry, and physics classes. In addition, new modules in three major content areas (earth and space science, physical science, and biological science) have been introduced to selected 6-8 grade science teachers in the summer of 2013. The NICE modules employ five E's of the learning cycle: Engage, Explore, Explain, Extend and Evaluate. Modules learning activities include field data collection, laboratory measurements, and data visualization and interpretation. Teachers are trained in the use of these modules for their classroom through unique partnership with Alabama Science in Motion (ASIM) and the Alabama Math Science Technology Initiative (AMSTI). Certified AMSTI teachers attend summer professional development workshops taught by ASIM and AMSTI specialists to learn to use NICE modules. During the school year, the specialists in turn deliver the needed equipment to conduct NICE classroom exercises and serve as an in-classroom resource for teachers and their students. Scientists are partnered with learning and teaching specialists and lead teachers to implement and test efficacy of instructional materials, models, and NASA data used in classroom. The assessment by professional evaluators after the development of the modules and the training of teachers indicates that the modules are complete, clear, and user-friendly. The overall teacher satisfaction from the teacher training was 4.88/5.00. After completing the module teacher training, the teachers reported a strong agreement that the content developed in the NICE modules should be included in the Alabama secondary curriculum. Eventually, the NICE program has the potential to reach over 200,000 students when the modules are fully implemented in every school in the state of Alabama. The project can give these students access to expertise and equipment, thereby strengthening the connections between the universities, state education administrators, and the community.

Design of multifunction anti-terrorism robotic system based on police dog

NASA Astrophysics Data System (ADS)

You, Bo; Liu, Suju; Xu, Jun; Li, Dongjie

2007-11-01

Aimed at some typical constraints of police dogs and robots used in the areas of reconnaissance and counterterrorism currently, the multifunction anti-terrorism robotic system based on police dog has been introduced. The system is made up of two parts: portable commanding device and police dog robotic system. The portable commanding device consists of power supply module, microprocessor module, LCD display module, wireless data receiving and dispatching module and commanding module, which implements the remote control to the police dogs and takes real time monitor to the video and images. The police dog robotic system consists of microprocessor module, micro video module, wireless data transmission module, power supply module and offence weapon module, which real time collects and transmits video and image data of the counter-terrorism sites, and gives military attack based on commands. The system combines police dogs' biological intelligence with micro robot. Not only does it avoid the complexity of general anti-terrorism robots' mechanical structure and the control algorithm, but it also widens the working scope of police dog, which meets the requirements of anti-terrorism in the new era.

Elemental Education.

ERIC Educational Resources Information Center

Daniel, Esther Gnanamalar Sarojini; Saat, Rohaida Mohd.

2001-01-01

Introduces a learning module integrating three disciplines--physics, chemistry, and biology--and based on four elements: carbon, oxygen, hydrogen, and silicon. Includes atomic model and silicon-based life activities. (YDS)

EPIGENETIC TRANSGENERATIONAL ACTIONS OF ENDOCRINE DISRUPTORS

PubMed Central

Skinner, Michael K.; Manikkam, Mohan; Guerrero-Bosagna, Carlos

2010-01-01

Environmental factors have a significant impact on biology. Therefore, environmental toxicants through similar mechanisms can modulate biological systems to influence physiology and promote disease states. The majority of environmental toxicants do not have the capacity to modulate DNA sequence, but can alter the epigenome. In the event an environmental toxicant such as an endocrine disruptor modifies the epigenome of a somatic cell, this may promote disease in the individual exposed, but not be transmitted to the next generation. In the event a toxicant modifies the epigenome of the germ line permanently, then the disease promoted can become transgenerationaly transmitted to subsequent progeny. The current review focuses on the ability of environmental factors such as endocrine disruptors to promote transgenerational phenotypes. PMID:21055462

atBioNet--an integrated network analysis tool for genomics and biomarker discovery.

PubMed

Ding, Yijun; Chen, Minjun; Liu, Zhichao; Ding, Don; Ye, Yanbin; Zhang, Min; Kelly, Reagan; Guo, Li; Su, Zhenqiang; Harris, Stephen C; Qian, Feng; Ge, Weigong; Fang, Hong; Xu, Xiaowei; Tong, Weida

2012-07-20

Large amounts of mammalian protein-protein interaction (PPI) data have been generated and are available for public use. From a systems biology perspective, Proteins/genes interactions encode the key mechanisms distinguishing disease and health, and such mechanisms can be uncovered through network analysis. An effective network analysis tool should integrate different content-specific PPI databases into a comprehensive network format with a user-friendly platform to identify key functional modules/pathways and the underlying mechanisms of disease and toxicity. atBioNet integrates seven publicly available PPI databases into a network-specific knowledge base. Knowledge expansion is achieved by expanding a user supplied proteins/genes list with interactions from its integrated PPI network. The statistically significant functional modules are determined by applying a fast network-clustering algorithm (SCAN: a Structural Clustering Algorithm for Networks). The functional modules can be visualized either separately or together in the context of the whole network. Integration of pathway information enables enrichment analysis and assessment of the biological function of modules. Three case studies are presented using publicly available disease gene signatures as a basis to discover new biomarkers for acute leukemia, systemic lupus erythematosus, and breast cancer. The results demonstrated that atBioNet can not only identify functional modules and pathways related to the studied diseases, but this information can also be used to hypothesize novel biomarkers for future analysis. atBioNet is a free web-based network analysis tool that provides a systematic insight into proteins/genes interactions through examining significant functional modules. The identified functional modules are useful for determining underlying mechanisms of disease and biomarker discovery. It can be accessed at: http://www.fda.gov/ScienceResearch/BioinformaticsTools/ucm285284.htm.

Radiogenomics of hepatocellular carcinoma: multiregion analysis-based identification of prognostic imaging biomarkers by integrating gene data—a preliminary study

NASA Astrophysics Data System (ADS)

Xia, Wei; Chen, Ying; Zhang, Rui; Yan, Zhuangzhi; Zhou, Xiaobo; Zhang, Bo; Gao, Xin

2018-02-01

Our objective was to identify prognostic imaging biomarkers for hepatocellular carcinoma in contrast-enhanced computed tomography (CECT) with biological interpretations by associating imaging features and gene modules. We retrospectively analyzed 371 patients who had gene expression profiles. For the 38 patients with CECT imaging data, automatic intra-tumor partitioning was performed, resulting in three spatially distinct subregions. We extracted a total of 37 quantitative imaging features describing intensity, geometry, and texture from each subregion. Imaging features were selected after robustness and redundancy analysis. Gene modules acquired from clustering were chosen for their prognostic significance. By constructing an association map between imaging features and gene modules with Spearman rank correlations, the imaging features that significantly correlated with gene modules were obtained. These features were evaluated with Cox’s proportional hazard models and Kaplan-Meier estimates to determine their prognostic capabilities for overall survival (OS). Eight imaging features were significantly correlated with prognostic gene modules, and two of them were associated with OS. Among these, the geometry feature volume fraction of the subregion, which was significantly correlated with all prognostic gene modules representing cancer-related interpretation, was predictive of OS (Cox p  =  0.022, hazard ratio  =  0.24). The texture feature cluster prominence in the subregion, which was correlated with the prognostic gene module representing lipid metabolism and complement activation, also had the ability to predict OS (Cox p  =  0.021, hazard ratio  =  0.17). Imaging features depicting the volume fraction and textural heterogeneity in subregions have the potential to be predictors of OS with interpretable biological meaning.

LifeSat engineering in-house vehicle design

NASA Technical Reports Server (NTRS)

Adkins, A.; Badhwar, G.; Bryant, L.; Caram, J.; Conley, G.; Crull, T.; Cuthbert, P.; Darcy, E.; Delaune, P.; Edeen, M.

1992-01-01

The LifeSat program was initiated to research the effects of microgravity and cosmic radiation on living organisms. The effects of long-term human exposure to free-space radiation fields over a range of gravitational environments has long been recognized as one of the primary design uncertainties for human space exploration. A critical design issue in the radiation biology requirements was the lack of definition of the minimum radiation absorbed dosage required to produce statistically meaningful data. The Phase A study produced a spacecraft conceptual design resembling a Discoverer configuration with a total weight of approximately 2800 pounds that would carry a 525-pound payload module (45 inches in diameter and 36 inches long) and support up to 12 rodents and a general biology module supporting lower life forms for an on-orbit duration of up to 60 days. The phase B conceptual designs focused on gravitational biology requirements and only briefly addressed the design impacts of the shift toward radiobiological science that occurred during the latter half of the Phase B studies.

Evolving cell models for systems and synthetic biology.

PubMed

Cao, Hongqing; Romero-Campero, Francisco J; Heeb, Stephan; Cámara, Miguel; Krasnogor, Natalio

2010-03-01

This paper proposes a new methodology for the automated design of cell models for systems and synthetic biology. Our modelling framework is based on P systems, a discrete, stochastic and modular formal modelling language. The automated design of biological models comprising the optimization of the model structure and its stochastic kinetic constants is performed using an evolutionary algorithm. The evolutionary algorithm evolves model structures by combining different modules taken from a predefined module library and then it fine-tunes the associated stochastic kinetic constants. We investigate four alternative objective functions for the fitness calculation within the evolutionary algorithm: (1) equally weighted sum method, (2) normalization method, (3) randomly weighted sum method, and (4) equally weighted product method. The effectiveness of the methodology is tested on four case studies of increasing complexity including negative and positive autoregulation as well as two gene networks implementing a pulse generator and a bandwidth detector. We provide a systematic analysis of the evolutionary algorithm's results as well as of the resulting evolved cell models.

Modifying the 5'-Cap for Click Reactions of Eukaryotic mRNA and To Tune Translation Efficiency in Living Cells.

PubMed

Holstein, Josephin M; Anhäuser, Lea; Rentmeister, Andrea

2016-08-26

The 5'-cap is a hallmark of eukaryotic mRNAs and plays fundamental roles in RNA metabolism, ranging from quality control to export and translation. Modifying the 5'-cap may thus enable modulation of the underlying processes and investigation or tuning of several biological functions. A straightforward approach is presented for the efficient production of a range of N7-modified caps based on the highly promiscuous methyltransferase Ecm1. We show that these, as well as N(2) -modified 5'-caps, can be used to tune translation of the respective mRNAs both in vitro and in cells. Appropriate modifications allow subsequent bioorthogonal chemistry, as demonstrated by intracellular live-cell labeling of a target mRNA. The efficient and versatile N7 manipulation of the mRNA cap makes mRNAs amenable to both modulation of their biological function and intracellular labeling, and represents a valuable addition to the chemical biology toolbox. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

X-ray micro-modulated luminescence tomography (XMLT)

PubMed Central

Cong, Wenxiang; Liu, Fenglin; Wang, Chao; Wang, Ge

2014-01-01

Imaging depth of optical microscopy has been fundamentally limited to millimeter or sub-millimeter due to strong scattering of light in a biological sample. X-ray microscopy can resolve spatial details of few microns deep inside a sample but contrast resolution is inadequate to depict heterogeneous features at cellular or sub-cellular levels. To enhance and enrich biological contrast at large imaging depth, various nanoparticles are introduced and become essential to basic research and molecular medicine. Nanoparticles can be functionalized as imaging probes, similar to fluorescent and bioluminescent proteins. LiGa5O8:Cr3+ nanoparticles were recently synthesized to facilitate luminescence energy storage with x-ray pre-excitation and subsequently stimulated luminescence emission by visible/near-infrared (NIR) light. In this paper, we propose an x-ray micro-modulated luminescence tomography (XMLT, or MLT to be more general) approach to quantify a nanophosphor distribution in a thick biological sample with high resolution. Our numerical simulation studies demonstrate the feasibility of the proposed approach. PMID:24663898

TinkerCell: modular CAD tool for synthetic biology.

PubMed

Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M

2009-10-29

Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD) is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks. An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API). TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at http://www.tinkercell.com. An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled and analyzed computationally. TinkerCell can readily accept third-party algorithms, allowing it to serve as a platform for testing different methods relevant to synthetic biology.

TinkerCell: modular CAD tool for synthetic biology

PubMed Central

Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M

2009-01-01

Background Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD) is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks. Results An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API). TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at . Conclusion An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled and analyzed computationally. TinkerCell can readily accept third-party algorithms, allowing it to serve as a platform for testing different methods relevant to synthetic biology. PMID:19874625

Apollo 14 and apollo 16 heavy-particle dosimetry experiments.

PubMed

Fleischer, R L; Hart, H R; Comstock, G M; Carter, M; Renshaw, A; Hardy, A

1973-08-03

Doses of heavy particles at positions inside the command modules of Apollo missions 8, 12, 14, and 16 correlate well with the calculated effects of solar modulation of the primary cosmic radiation. Differences in doses at different stowage positions indicate that the redistribution of mass within the spacecraft could enhance safety from the biological damage that would otherwise be expected on manned, deep-space missions.

Towards the Structure Determination of a Modulated Protein Crystal: The Semicrystalline State of Profilin:Actin

NASA Technical Reports Server (NTRS)

Borgstahl, G.; Lovelace, J.; Snell, E. H.; Bellamy, H.

2003-01-01

One of the remaining challenges to structural biology is the solution of modulated structures. While small molecule crystallographers have championed this type of structure, to date, no modulated macromolecular structures have been determined. Modulation of the molecular structures within the crystal can produce satellite reflections or a superlattice of reflections in reciprocal space. We have developed the data collection methods and strategies that are needed to collect and analyze these data. If the macromolecule's crystal lattice is composed of physiologically relevant packing contacts, structural changes induced under physiological conditions can cause distortion relevant to the function and biophysical processes of the molecule making up the crystal. By careful measurement of the distortion, and the corresponding three-dimensional structure of the distorted molecule, we will visualize the motion and mechanism of the biological macromolecule(s). We have measured the modulated diffraction pattern produced by the semicrystalline state of profilin:actin crystals using highly parallel and highly monochromatic synchrotron radiation coupled with fine phi slicing (0.001-0.010 degrees) for structure determination. These crystals present these crystals present a unique opportunity to address an important question in structural biology. The modulation is believed to be due to the formation of actin helical filaments from the actin beta ribbon upon the pH-induced dissociation of profilin. To date, the filamentous state of actin has resisted crystallization and no detailed structures are available. The semicrystalline state profilin:actin crystals provides a unique opportunity to understand the many conformational states of actin. This knowledge is essential for understanding the dynamics underlying shape changes and motility of eukaryotic cells. Many essential processes, such as cytokinesis, phagocytosis, and cellular migration depend upon the capacity of the actin microfilament system to be restructured in a controlled manner via polymerization, depolymerization, severing, cross-linking, and anchorage. The structure the semicrystalline state of profilin:actin will challenge and validate current models of muscle contraction and cell motility. The methodology and theory under development will be easily extendable to other systems.

Computer-aided design of biological circuits using TinkerCell

PubMed Central

Bergmann, Frank T; Sauro, Herbert M

2010-01-01

Synthetic biology is an engineering discipline that builds on modeling practices from systems biology and wet-lab techniques from genetic engineering. As synthetic biology advances, efficient procedures will be developed that will allow a synthetic biologist to design, analyze and build biological networks. In this idealized pipeline, computer-aided design (CAD) is a necessary component. The role of a CAD application would be to allow efficient transition from a general design to a final product. TinkerCell is a design tool for serving this purpose in synthetic biology. In TinkerCell, users build biological networks using biological parts and modules. The network can be analyzed using one of several functions provided by TinkerCell or custom programs from third-party sources. Since best practices for modeling and constructing synthetic biology networks have not yet been established, TinkerCell is designed as a flexible and extensible application that can adjust itself to changes in the field. PMID:21327060

Metabolomics: Definitions and Significance in Systems Biology.

PubMed

Klassen, Aline; Faccio, Andréa Tedesco; Canuto, Gisele André Baptista; da Cruz, Pedro Luis Rocha; Ribeiro, Henrique Caracho; Tavares, Marina Franco Maggi; Sussulini, Alessandra

2017-01-01

Nowadays, there is a growing interest in deeply understanding biological mechanisms not only at the molecular level (biological components) but also the effects of an ongoing biological process in the organism as a whole (biological functionality), as established by the concept of systems biology. Within this context, metabolomics is one of the most powerful bioanalytical strategies that allow obtaining a picture of the metabolites of an organism in the course of a biological process, being considered as a phenotyping tool. Briefly, metabolomics approach consists in identifying and determining the set of metabolites (or specific metabolites) in biological samples (tissues, cells, fluids, or organisms) under normal conditions in comparison with altered states promoted by disease, drug treatment, dietary intervention, or environmental modulation. The aim of this chapter is to review the fundamentals and definitions used in the metabolomics field, as well as to emphasize its importance in systems biology and clinical studies.

Stochastic Blockmodeling of the Modules and Core of the Caenorhabditis elegans Connectome

PubMed Central

Pavlovic, Dragana M.; Vértes, Petra E.; Bullmore, Edward T.; Schafer, William R.; Nichols, Thomas E.

2014-01-01

Recently, there has been much interest in the community structure or mesoscale organization of complex networks. This structure is characterised either as a set of sparsely inter-connected modules or as a highly connected core with a sparsely connected periphery. However, it is often difficult to disambiguate these two types of mesoscale structure or, indeed, to summarise the full network in terms of the relationships between its mesoscale constituents. Here, we estimate a community structure with a stochastic blockmodel approach, the Erdős-Rényi Mixture Model, and compare it to the much more widely used deterministic methods, such as the Louvain and Spectral algorithms. We used the Caenorhabditis elegans (C. elegans) nervous system (connectome) as a model system in which biological knowledge about each node or neuron can be used to validate the functional relevance of the communities obtained. The deterministic algorithms derived communities with 4–5 modules, defined by sparse inter-connectivity between all modules. In contrast, the stochastic Erdős-Rényi Mixture Model estimated a community with 9 blocks or groups which comprised a similar set of modules but also included a clearly defined core, made of 2 small groups. We show that the “core-in-modules” decomposition of the worm brain network, estimated by the Erdős-Rényi Mixture Model, is more compatible with prior biological knowledge about the C. elegans nervous system than the purely modular decomposition defined deterministically. We also show that the blockmodel can be used both to generate stochastic realisations (simulations) of the biological connectome, and to compress network into a small number of super-nodes and their connectivity. We expect that the Erdős-Rényi Mixture Model may be useful for investigating the complex community structures in other (nervous) systems. PMID:24988196

Evaluation of Formative Computer-Based Assessment by Cell Biology Students with Differing Entry Qualifications and Ethnicity

ERIC Educational Resources Information Center

Bax, Christopher; Baggott, Glenn; Howey, Ellen; Pellet-Many, Carolyn; Rayne, Richard; Neonaki, Maria; Bax, Bridget E.; White, Christopher Branford

2006-01-01

This study was carried out to examine students' responses to the use of on-line assessments that included feedback. First year BSc students taking a Cell Biology module undertook such an assessment and were then asked to evaluate the test by completing an anonymous questionnaire. Answers were analysed in light of the respondents' ethnicity and…

The Effectiveness of a Case Study-Based First-Year Biology Class at a Black Women's College

ERIC Educational Resources Information Center

Pai, Aditi; Benning, Tracy; Woods, Natasha; McGinnis, Gene; Chu, Joanne; Netherton, Josh; Bauerle, Cynthia

2010-01-01

The authors used a case study-based approach in the introductory biology course at Spelman College. The course taught to entering freshmen was divided into three modules--ecology, evolution, and biodiversity, each designed around a case study. They noted that (1) case study teaching was dramatically more effective than the traditional lecture…

Preparation, Purification, and Secondary Structure Determination of Bacillus Circulans Xylanase. A Molecular Laboratory Incorporating Aspects of Molecular Biology, Biochemistry, and Biophysical Chemistry

ERIC Educational Resources Information Center

Russo, Sal; Gentile, Lisa

2006-01-01

A project module designed for biochemistry or cellular and molecular biology student which involves determining the secondary structure of Bacillus circulans xylanase (BCX) by circular dichroism (CD) spectroscopy under conditions that compromise its stabilizing intramolecular forces is described. The lab model enhanced students knowledge of the…

Moving Away from Dogmatic Knowledge Dissemination in a Cell Biology Module: Examples from Singapore

ERIC Educational Resources Information Center

Yeong, Foong May

2012-01-01

A surge in the amount of information in the discipline of Cell Biology presents a problem to the teaching of undergraduates under time constraints. In most textbooks and during lectures, students in Singapore are often taught in a dogmatic manner where concepts and ideas are expounded to them. The students in turn passively receive the materials…

Pan-phylum Comparison of Nematode Metabolic Potential

PubMed Central

Tyagi, Rahul; Rosa, Bruce A.; Lewis, Warren G.; Mitreva, Makedonka

2015-01-01

Nematodes are among the most important causative pathogens of neglected tropical diseases. The increased availability of genomic and transcriptomic data for many understudied nematode species provides a great opportunity to investigate different aspects of their biology. Increasingly, metabolic potential of pathogens is recognized as a critical determinant governing their development, growth and pathogenicity. Comparing metabolic potential among species with distinct trophic ecologies can provide insights on overall biology or molecular adaptations. Furthermore, ascertaining gene expression at pathway level can help in understanding metabolic dynamics over development. Comparison of biochemical pathways (or subpathways, i.e. pathway modules) among related species can also retrospectively indicate potential mistakes in gene-calling and functional annotation. We show with numerous illustrative case studies that comparisons at the level of pathway modules have the potential to uncover biological insights while remaining computationally tractable. Here, we reconstruct and compare metabolic modules found in the deduced proteomes of 13 nematodes and 10 non-nematode species (including hosts of the parasitic nematode species). We observed that the metabolic potential is, in general, concomitant with phylogenetic and/or ecological similarity. Varied metabolic strategies are required among the nematodes, with only 8 out of 51 pathway modules being completely conserved. Enzyme comparison based on topology of metabolic modules uncovered diversification between parasite and host that can potentially guide therapeutic intervention. Gene expression data from 4 nematode species were used to study metabolic dynamics over their life cycles. We report unexpected differential metabolism between immature and mature microfilariae of the human filarial parasite Brugia malayi. A set of genes potentially important for parasitism is also reported, based on an analysis of gene expression in C. elegans and the human hookworm Necator americanus. We illustrate how analyzing and comparing metabolism at the level of pathway modules can improve existing knowledge of nematode metabolic potential and can provide parasitism related insights. Our reconstruction and comparison of nematode metabolic pathways at a pan-phylum and inter-phylum level enabled determination of phylogenetic restrictions and differential expression of pathways. A visualization of our results is available at http://nematode.net and the program for identification of module completeness (modDFS) is freely available at SourceForge. The methods reported will help biologists to predict biochemical potential of any organism with available deduced proteome, to direct experiments and test hypotheses. PMID:26000881

A Gene Module-Based eQTL Analysis Prioritizing Disease Genes and Pathways in Kidney Cancer.

PubMed

Yang, Mary Qu; Li, Dan; Yang, William; Zhang, Yifan; Liu, Jun; Tong, Weida

2017-01-01

Clear cell renal cell carcinoma (ccRCC) is the most common and most aggressive form of renal cell cancer (RCC). The incidence of RCC has increased steadily in recent years. The pathogenesis of renal cell cancer remains poorly understood. Many of the tumor suppressor genes, oncogenes, and dysregulated pathways in ccRCC need to be revealed for improvement of the overall clinical outlook of the disease. Here, we developed a systems biology approach to prioritize the somatic mutated genes that lead to dysregulation of pathways in ccRCC. The method integrated multi-layer information to infer causative mutations and disease genes. First, we identified differential gene modules in ccRCC by coupling transcriptome and protein-protein interactions. Each of these modules consisted of interacting genes that were involved in similar biological processes and their combined expression alterations were significantly associated with disease type. Then, subsequent gene module-based eQTL analysis revealed somatic mutated genes that had driven the expression alterations of differential gene modules. Our study yielded a list of candidate disease genes, including several known ccRCC causative genes such as BAP1 and PBRM1 , as well as novel genes such as NOD2, RRM1, CSRNP1, SLC4A2, TTLL1 and CNTN1. The differential gene modules and their driver genes revealed by our study provided a new perspective for understanding the molecular mechanisms underlying the disease. Moreover, we validated the results in independent ccRCC patient datasets. Our study provided a new method for prioritizing disease genes and pathways.

Atypical biological motion kinematics are represented by complementary lower-level and top-down processes during imitation learning.

PubMed

Hayes, Spencer J; Dutoy, Chris A; Elliott, Digby; Gowen, Emma; Bennett, Simon J

2016-01-01

Learning a novel movement requires a new set of kinematics to be represented by the sensorimotor system. This is often accomplished through imitation learning where lower-level sensorimotor processes are suggested to represent the biological motion kinematics associated with an observed movement. Top-down factors have the potential to influence this process based on the social context, attention and salience, and the goal of the movement. In order to further examine the potential interaction between lower-level and top-down processes in imitation learning, the aim of this study was to systematically control the mediating effects during an imitation of biological motion protocol. In this protocol, we used non-human agent models that displayed different novel atypical biological motion kinematics, as well as a control model that displayed constant velocity. Importantly the three models had the same movement amplitude and movement time. Also, the motion kinematics were displayed in the presence, or absence, of end-state-targets. Kinematic analyses showed atypical biological motion kinematics were imitated, and that this performance was different from the constant velocity control condition. Although the imitation of atypical biological motion kinematics was not modulated by the end-state-targets, movement time was more accurate in the absence, compared to the presence, of an end-state-target. The fact that end-state targets modulated movement time accuracy, but not biological motion kinematics, indicates imitation learning involves top-down attentional, and lower-level sensorimotor systems, which operate as complementary processes mediated by the environmental context. Copyright © 2015 Elsevier B.V. All rights reserved.

RM-SORN: a reward-modulated self-organizing recurrent neural network.

PubMed

Aswolinskiy, Witali; Pipa, Gordon

2015-01-01

Neural plasticity plays an important role in learning and memory. Reward-modulation of plasticity offers an explanation for the ability of the brain to adapt its neural activity to achieve a rewarded goal. Here, we define a neural network model that learns through the interaction of Intrinsic Plasticity (IP) and reward-modulated Spike-Timing-Dependent Plasticity (STDP). IP enables the network to explore possible output sequences and STDP, modulated by reward, reinforces the creation of the rewarded output sequences. The model is tested on tasks for prediction, recall, non-linear computation, pattern recognition, and sequence generation. It achieves performance comparable to networks trained with supervised learning, while using simple, biologically motivated plasticity rules, and rewarding strategies. The results confirm the importance of investigating the interaction of several plasticity rules in the context of reward-modulated learning and whether reward-modulated self-organization can explain the amazing capabilities of the brain.

Fast wavefront optimization for focusing through biological tissue (Conference Presentation)

NASA Astrophysics Data System (ADS)

Blochet, Baptiste; Bourdieu, Laurent; Gigan, Sylvain

2017-02-01

The propagation of light in biological tissues is rapidly dominated by multiple scattering: ballistic light is exponentially attenuated, which limits the penetration depth of conventional microscopy techniques. For coherent light, the recombination of the different scattered paths creates a complex interference: speckle. Recently, different wavefront shaping techniques have been developed to coherently manipulate the speckle. It opens the possibility to focus light through complex media and ultimately to image in them, provided however that the medium can be considered as stationary. We have studied the possibility to focus in and through time-varying biological tissues. Their intrinsic temporal dynamics creates a fast decorrelation of the speckle pattern. Therefore, focusing through biological tissues requires fast wavefront shaping devices, sensors and algorithms. We have investigated the use of a MEMS-based spatial light modulator (SLM) and a fast photodetector, combined with FPGA electronics to implement a closed-loop optimization. Our optimization process is just limited by the temporal dynamics of the SLM (200µs) and the computation time (45µs), thus corresponding to a rate of 4 kHz. To our knowledge, it's the fastest closed loop optimization using phase modulators. We have studied the focusing through colloidal solutions of TiO2 particles in glycerol, allowing tunable temporal stability, and scattering properties similar to biological tissues. We have shown that our set-up fulfills the required characteristics (speed, enhancement) to focus through biological tissues. We are currently investigating the focusing through acute rat brain slices and the memory effect in dynamic scattering media.

Inborn errors of metabolism and the human interactome: a systems medicine approach.

PubMed

Woidy, Mathias; Muntau, Ania C; Gersting, Søren W

2018-02-05

The group of inborn errors of metabolism (IEM) displays a marked heterogeneity and IEM can affect virtually all functions and organs of the human organism; however, IEM share that their associated proteins function in metabolism. Most proteins carry out cellular functions by interacting with other proteins, and thus are organized in biological networks. Therefore, diseases are rarely the consequence of single gene mutations but of the perturbations caused in the related cellular network. Systematic approaches that integrate multi-omics and database information into biological networks have successfully expanded our knowledge of complex disorders but network-based strategies have been rarely applied to study IEM. We analyzed IEM on a proteome scale and found that IEM-associated proteins are organized as a network of linked modules within the human interactome of protein interactions, the IEM interactome. Certain IEM disease groups formed self-contained disease modules, which were highly interlinked. On the other hand, we observed disease modules consisting of proteins from many different disease groups in the IEM interactome. Moreover, we explored the overlap between IEM and non-IEM disease genes and applied network medicine approaches to investigate shared biological pathways, clinical signs and symptoms, and links to drug targets. The provided resources may help to elucidate the molecular mechanisms underlying new IEM, to uncover the significance of disease-associated mutations, to identify new biomarkers, and to develop novel therapeutic strategies.

Tripal v1.1: a standards-based toolkit for construction of online genetic and genomic databases.

PubMed

Sanderson, Lacey-Anne; Ficklin, Stephen P; Cheng, Chun-Huai; Jung, Sook; Feltus, Frank A; Bett, Kirstin E; Main, Dorrie

2013-01-01

Tripal is an open-source freely available toolkit for construction of online genomic and genetic databases. It aims to facilitate development of community-driven biological websites by integrating the GMOD Chado database schema with Drupal, a popular website creation and content management software. Tripal provides a suite of tools for interaction with a Chado database and display of content therein. The tools are designed to be generic to support the various ways in which data may be stored in Chado. Previous releases of Tripal have supported organisms, genomic libraries, biological stocks, stock collections and genomic features, their alignments and annotations. Also, Tripal and its extension modules provided loaders for commonly used file formats such as FASTA, GFF, OBO, GAF, BLAST XML, KEGG heir files and InterProScan XML. Default generic templates were provided for common views of biological data, which could be customized using an open Application Programming Interface to change the way data are displayed. Here, we report additional tools and functionality that are part of release v1.1 of Tripal. These include (i) a new bulk loader that allows a site curator to import data stored in a custom tab delimited format; (ii) full support of every Chado table for Drupal Views (a powerful tool allowing site developers to construct novel displays and search pages); (iii) new modules including 'Feature Map', 'Genetic', 'Publication', 'Project', 'Contact' and the 'Natural Diversity' modules. Tutorials, mailing lists, download and set-up instructions, extension modules and other documentation can be found at the Tripal website located at http://tripal.info. DATABASE URL: http://tripal.info/.

Tripal v1.1: a standards-based toolkit for construction of online genetic and genomic databases

PubMed Central

Sanderson, Lacey-Anne; Ficklin, Stephen P.; Cheng, Chun-Huai; Jung, Sook; Feltus, Frank A.; Bett, Kirstin E.; Main, Dorrie

2013-01-01

Tripal is an open-source freely available toolkit for construction of online genomic and genetic databases. It aims to facilitate development of community-driven biological websites by integrating the GMOD Chado database schema with Drupal, a popular website creation and content management software. Tripal provides a suite of tools for interaction with a Chado database and display of content therein. The tools are designed to be generic to support the various ways in which data may be stored in Chado. Previous releases of Tripal have supported organisms, genomic libraries, biological stocks, stock collections and genomic features, their alignments and annotations. Also, Tripal and its extension modules provided loaders for commonly used file formats such as FASTA, GFF, OBO, GAF, BLAST XML, KEGG heir files and InterProScan XML. Default generic templates were provided for common views of biological data, which could be customized using an open Application Programming Interface to change the way data are displayed. Here, we report additional tools and functionality that are part of release v1.1 of Tripal. These include (i) a new bulk loader that allows a site curator to import data stored in a custom tab delimited format; (ii) full support of every Chado table for Drupal Views (a powerful tool allowing site developers to construct novel displays and search pages); (iii) new modules including ‘Feature Map’, ‘Genetic’, ‘Publication’, ‘Project’, ‘Contact’ and the ‘Natural Diversity’ modules. Tutorials, mailing lists, download and set-up instructions, extension modules and other documentation can be found at the Tripal website located at http://tripal.info. Database URL: http://tripal.info/ PMID:24163125

Microrobots for in vitro fertilization applications.

PubMed

Boukallel, M; Gauthier, M; Piat, E; Abadie, J; Roux, C

2004-05-01

The Micromanipulation and Micro-actuation Research Group at the LAB has activities related to biological and surgical applications. Concerning cells micromanipulation, our laboratory works in collaboration with the research team "Genetic and Reproduction" of the Besançon's hospital (France). The global final objective is the development of an automatic intra cytoplasmic sperm injection (ICSI) device in order to improve performances and ergonomics of current devices. In the future this new device will contain various modules: module for removal of cumulus cells, modules for characterization of oocytes, microinjection module, cells transport system. The first subsystem developed is a new single cell transport system. It consists in a so-called micropusher which pushes single cells without having contact with the external environment. This micropusher is a ferromagnetic particle (from 400 x 400 x 20 microm3 to 100 x 100 x 5 microm3) which follows the movement of a permanent magnet located under the biological medium. A 2D micro-positioning table moves this magnet under the glass slide. The pusher and cells positions are measured through an optical microscope with a CCD camera located above the biological medium. The second subsystem is developed to measure oocytes mechanical stiffness in order to sort them. We have then developed a micro/nano-force sensor based on the diamagnetic levitation principle: a glass tip end-effector (with 20 microm in diameter) is fixed on the equipment which is in levitation (0.5 mm in diameter, 100 mm in length). When a force is applied to the levitated glass tip, it moves to a new equilibrium position. Thanks to themeasurement of this displacement, the applied force can be measured. Since there is no contact and friction between the levitated tip and the fixed part, the resolution of this sensor is very high (10 nN).

Functional Module Search in Protein Networks based on Semantic Similarity Improves the Analysis of Proteomics Data*

PubMed Central

Boyanova, Desislava; Nilla, Santosh; Klau, Gunnar W.; Dandekar, Thomas; Müller, Tobias; Dittrich, Marcus

2014-01-01

The continuously evolving field of proteomics produces increasing amounts of data while improving the quality of protein identifications. Albeit quantitative measurements are becoming more popular, many proteomic studies are still based on non-quantitative methods for protein identification. These studies result in potentially large sets of identified proteins, where the biological interpretation of proteins can be challenging. Systems biology develops innovative network-based methods, which allow an integrated analysis of these data. Here we present a novel approach, which combines prior knowledge of protein-protein interactions (PPI) with proteomics data using functional similarity measurements of interacting proteins. This integrated network analysis exactly identifies network modules with a maximal consistent functional similarity reflecting biological processes of the investigated cells. We validated our approach on small (H9N2 virus-infected gastric cells) and large (blood constituents) proteomic data sets. Using this novel algorithm, we identified characteristic functional modules in virus-infected cells, comprising key signaling proteins (e.g. the stress-related kinase RAF1) and demonstrate that this method allows a module-based functional characterization of cell types. Analysis of a large proteome data set of blood constituents resulted in clear separation of blood cells according to their developmental origin. A detailed investigation of the T-cell proteome further illustrates how the algorithm partitions large networks into functional subnetworks each representing specific cellular functions. These results demonstrate that the integrated network approach not only allows a detailed analysis of proteome networks but also yields a functional decomposition of complex proteomic data sets and thereby provides deeper insights into the underlying cellular processes of the investigated system. PMID:24807868

Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

PubMed

Gonçalves, Joana P; Aires, Ricardo S; Francisco, Alexandre P; Madeira, Sara C

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched processes related to these biological events were identified. Ranking scores further suggested ability to discern the primary role of a gene (target or regulator). Prototype is available at: http://kdbio.inesc-id.pt/software/regulatorysnapshots.

Regulatory Snapshots: Integrative Mining of Regulatory Modules from Expression Time Series and Regulatory Networks

PubMed Central

Gonçalves, Joana P.; Aires, Ricardo S.; Francisco, Alexandre P.; Madeira, Sara C.

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched processes related to these biological events were identified. Ranking scores further suggested ability to discern the primary role of a gene (target or regulator). Prototype is available at: http://kdbio.inesc-id.pt/software/regulatorysnapshots. PMID:22563474

Multifunctional ferromagnetic disks for modulating cell function

PubMed Central

Vitol, Elina A.; Novosad, Valentyn; Rozhkova, Elena A.

2013-01-01

In this work, we focus on the methods for controlling cell function with ferromagnetic disk-shaped particles. We will first review the history of magnetically assisted modulation of cell behavior and applications of magnetic particles for studying physical properties of a cell. Then, we consider the biological applications of the microdisks such as the method for induction of cancer cell apoptosis, controlled drug release, hyperthermia and MRI imaging. PMID:23766544

Broad-host-range vector system for synthetic biology and biotechnology in cyanobacteria

PubMed Central

Taton, Arnaud; Unglaub, Federico; Wright, Nicole E.; Zeng, Wei Yue; Paz-Yepes, Javier; Brahamsha, Bianca; Palenik, Brian; Peterson, Todd C.; Haerizadeh, Farzad; Golden, Susan S.; Golden, James W.

2014-01-01

Inspired by the developments of synthetic biology and the need for improved genetic tools to exploit cyanobacteria for the production of renewable bioproducts, we developed a versatile platform for the construction of broad-host-range vector systems. This platform includes the following features: (i) an efficient assembly strategy in which modules released from 3 to 4 donor plasmids or produced by polymerase chain reaction are assembled by isothermal assembly guided by short GC-rich overlap sequences. (ii) A growing library of molecular devices categorized in three major groups: (a) replication and chromosomal integration; (b) antibiotic resistance; (c) functional modules. These modules can be assembled in different combinations to construct a variety of autonomously replicating plasmids and suicide plasmids for gene knockout and knockin. (iii) A web service, the CYANO-VECTOR assembly portal, which was built to organize the various modules, facilitate the in silico construction of plasmids, and encourage the use of this system. This work also resulted in the construction of an improved broad-host-range replicon derived from RSF1010, which replicates in several phylogenetically distinct strains including a new experimental model strain Synechocystis sp. WHSyn, and the characterization of nine antibiotic cassettes, four reporter genes, four promoters, and a ribozyme-based insulator in several diverse cyanobacterial strains. PMID:25074377

Responsive nanoporous metals: recoverable modulations on strength and shape by watering

NASA Astrophysics Data System (ADS)

Ye, Xing-Long; Liu, Ling-Zhi; Jin, Hai-Jun

2016-08-01

Many biological materials can readily modulate their mechanical properties and shape by interacting with water in the surrounding environment, which is essential to their high performance in application. In contrast, typical inorganic materials (such as the metals) cannot change their strength and shape without involving thermal/mechanical treatments. By introducing nano-scale porous structure and exploiting a simple physical concept—the water-capillarity in nanopores, here we report that a ‘dead’ metal can be transformed into a ‘smart’ material with water-responsive properties. We demonstrate that the apparent strength, volume and shape of nanoporous Au and Au(Pt) can be modulated in situ, dramatically and recoverably, in response to water-dipping and partial-drying. The amplitude of strength-modulation reaches 20 MPa, which is nearly 50% of the yield strength at initial state. This approach also leads to reversible length change up to 1.3% in nanoporous Au and a large reversible bending motion of a bi-layer strip with tip displacement of ˜20 mm, which may be used for actuation. This method is simple and effective, occurring in situ under ambient conditions and requiring no external power, analogous to biological materials. The findings may open up novel applications in many areas such as micro-robotics and bio-medical devices.

Using molecular functional networks to manifest connections between obesity and obesity-related diseases

PubMed Central

Yang, Jialiang; Qiu, Jing; Wang, Kejing; Zhu, Lijuan; Fan, Jingjing; Zheng, Deyin; Meng, Xiaodi; Yang, Jiasheng; Peng, Lihong; Fu, Yu; Zhang, Dahan; Peng, Shouneng; Huang, Haiyun; Zhang, Yi

2017-01-01

Obesity is a primary risk factor for many diseases such as certain cancers. In this study, we have developed three algorithms including a random-walk based method OBNet, a shortest-path based method OBsp and a direct-overlap method OBoverlap, to reveal obesity-disease connections at protein-interaction subnetworks corresponding to thousands of biological functions and pathways. Through literature mining, we also curated an obesity-associated disease list, by which we compared the methods. As a result, OBNet outperforms other two methods. OBNet can predict whether a disease is obesity-related based on its associated genes. Meanwhile, OBNet identifies extensive connections between obesity genes and genes associated with a few diseases at various functional modules and pathways. Using breast cancer and Type 2 diabetes as two examples, OBNet identifies meaningful genes that may play key roles in connecting obesity and the two diseases. For example, TGFB1 and VEGFA are inferred to be the top two key genes mediating obesity-breast cancer connection in modules associated with brain development. Finally, the top modules identified by OBNet in breast cancer significantly overlap with modules identified from TCGA breast cancer gene expression study, revealing the power of OBNet in identifying biological processes involved in the disease. PMID:29156709

Highly preserved consensus gene modules in human papilloma virus 16 positive cervical cancer and head and neck cancers.

PubMed

Zhang, Xianglan; Cha, In-Ho; Kim, Ki-Yeol

2017-12-26

In this study, we investigated the consensus gene modules in head and neck cancer (HNC) and cervical cancer (CC). We used a publicly available gene expression dataset, GSE6791, which included 42 HNC, 14 normal head and neck, 20 CC and 8 normal cervical tissue samples. To exclude bias because of different human papilloma virus (HPV) types, we analyzed HPV16-positive samples only. We identified 3824 genes common to HNC and CC samples. Among these, 977 genes showed high connectivity and were used to construct consensus modules. We demonstrated eight consensus gene modules for HNC and CC using the dissimilarity measure and average linkage hierarchical clustering methods. These consensus modules included genes with significant biological functions, including ATP binding and extracellular exosome. Eigengen network analysis revealed the consensus modules were highly preserved with high connectivity. These findings demonstrate that HPV16-positive head and neck and cervical cancers share highly preserved consensus gene modules with common potentially therapeutic targets.

Wide-field imaging through scattering media by scattered light fluorescence microscopy

NASA Astrophysics Data System (ADS)

Zhou, Yulan; Li, Xun

2017-08-01

To obtain images through scattering media, scattered light fluorescence (SLF) microscopy that utilizes the optical memory effect has been developed. However, the small field of view (FOV) of SLF microscopy limits its application. In this paper, we have introduced a re-modulation method to achieve wide-field imaging through scattering media by SLF microscopy. In the re-modulation method, to raster scan the focus across the object plane, the incident wavefront is re-modulated via a spatial light modulator (SLM) in the updated phase compensation calculated using the optimized iterative algorithm. Compared with the conventional optical memory effect method, the re-modulation method can greatly increase the FOV of a SLF microscope. With the phase compensation theoretically calculated, the process of updating the phase compensation of a high speed SLM is fast. The re-modulation method does not increase the imaging time. The re-modulation method is, therefore, expected to make SLF microscopy have much wider applications in biology, medicine and physiology.

Insight into structural requirements for selective and/or dual CXCR3 and CXCR4 allosteric modulators.

PubMed

Kolarič, Anja; Švajger, Urban; Tomašič, Tihomir; Brox, Regine; Frank, Theresa; Minovski, Nikola; Tschammer, Nuska; Anderluh, Marko

2018-05-11

Based on the previously published pyrazolopyridine-based hit compound for which negative allosteric modulation of both CXCR3 and CXCR4 receptors was disclosed, we designed, synthesized and biologically evaluated a set of novel, not only negative, but also positive allosteric modulators with preserved pyrazolopyridine core. Compound 9e is a dual negative modulator, inhibiting G protein activity of both receptors. For CXCR4 receptor para-substituted aromatic group of compounds distinguishes between negative and positive modulation. Para-methoxy substitution leads to functional antagonism, while para-chloro triggers agonism. Additionally, we discovered that chemotaxis is not completely correlated with G protein pathways. This is the first work in which we have on a series of compounds successfully demonstrated that it is possible to produce selective as well as dual-acting modulators of chemokine receptors, which is very promising for future research in the field of discovery of selective or dual modulators of chemokine receptors. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Highly preserved consensus gene modules in human papilloma virus 16 positive cervical cancer and head and neck cancers

PubMed Central

Zhang, Xianglan; Cha, In-Ho; Kim, Ki-Yeol

2017-01-01

In this study, we investigated the consensus gene modules in head and neck cancer (HNC) and cervical cancer (CC). We used a publicly available gene expression dataset, GSE6791, which included 42 HNC, 14 normal head and neck, 20 CC and 8 normal cervical tissue samples. To exclude bias because of different human papilloma virus (HPV) types, we analyzed HPV16-positive samples only. We identified 3824 genes common to HNC and CC samples. Among these, 977 genes showed high connectivity and were used to construct consensus modules. We demonstrated eight consensus gene modules for HNC and CC using the dissimilarity measure and average linkage hierarchical clustering methods. These consensus modules included genes with significant biological functions, including ATP binding and extracellular exosome. Eigengen network analysis revealed the consensus modules were highly preserved with high connectivity. These findings demonstrate that HPV16-positive head and neck and cervical cancers share highly preserved consensus gene modules with common potentially therapeutic targets. PMID:29371966

Relative Biological Effectiveness Variation Along Monoenergetic and Modulated Bragg Peaks of a 62-MeV Therapeutic Proton Beam: A Preclinical Assessment

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

Chaudhary, Pankaj; Marshall, Thomas I.; Perozziello, Francesca M.

2014-09-01

Purpose: The biological optimization of proton therapy can be achieved only through a detailed evaluation of relative biological effectiveness (RBE) variations along the full range of the Bragg curve. The clinically used RBE value of 1.1 represents a broad average, which disregards the steep rise of linear energy transfer (LET) at the distal end of the spread-out Bragg peak (SOBP). With particular attention to the key endpoint of cell survival, our work presents a comparative investigation of cell killing RBE variations along monoenergetic (pristine) and modulated (SOBP) beams using human normal and radioresistant cells with the aim to investigate themore » RBE dependence on LET and intrinsic radiosensitvity. Methods and Materials: Human fibroblasts (AG01522) and glioma (U87) cells were irradiated at 6 depth positions along pristine and modulated 62-MeV proton beams at the INFN-LNS (Catania, Italy). Cell killing RBE variations were measured using standard clonogenic assays and were further validated using Monte Carlo simulations and the local effect model (LEM). Results: We observed significant cell killing RBE variations along the proton beam path, particularly in the distal region showing strong dose dependence. Experimental RBE values were in excellent agreement with the LEM predicted values, indicating dose-averaged LET as a suitable predictor of proton biological effectiveness. Data were also used to validate a parameterized RBE model. Conclusions: The predicted biological dose delivered to a tumor region, based on the variable RBE inferred from the data, varies significantly with respect to the clinically used constant RBE of 1.1. The significant RBE increase at the distal end suggests also a potential to enhance optimization of treatment modalities such as LET painting of hypoxic tumors. The study highlights the limitation of adoption of a constant RBE for proton therapy and suggests approaches for fast implementation of RBE models in treatment planning.« less

Animal protein production modules in biological life support systems: Novel combined aquaculture techniques based on the closed equilibrated biological aquatic system (C.E.B.A.S.)

NASA Astrophysics Data System (ADS)

Blüm, V.; Andriske, M.; Kreuzberg, K.; Schreibman, M. P.

Based on the experiences made with the Closed Equilibrated Biological Aquatic System (C.E.B.A.S.) which was primarily deveoloped for long-term and multi-generation experiments with aquatic animals and plants in a space station highly effective fresh water recycling modules were elaborated utilizing a combination of ammonia oxidizing bacteria filters and higher plants. These exhibit a high effectivity to eliminate phosphate and anorganic nitrogen compounds and arc. in addidition. able to contribute to the oxygen supply of the aquatic animals. The C.E.B.A.S. filter system is able to keep a closed artificial aquatic ecosystem containing teleost fishes and water snails biologically stable for several month and to eliminate waste products deriving from degraded dead fishes without a decrease of the oxygen concentration down to less than 3.5 mg/l at 25 °C. More advanced C.E.B.A.S. filter systems, the BIOCURE filters, were also developed for utilization in semiintensive and intensive aquaculture systems for fishes. In fact such combined animal-plant aquaculture systems represent highly effective productions sites for human food if proper plant and fish species are selected The present papers elucidates ways to novel aquaculture systems in which herbivorous fishes are raised by feeding them with plant biomass produced in the BIOCURE filters and presents the scheme of a modification which utilizes a plant species suitable also for human nutrition. Special attention is paid to the benefits of closed aquaculture system modules which may be integrated into bioregenerative life support systems of a higher complexity for, e. g.. lunar or planetary bases including some psychologiccal aspects of the introduction of animal protein production into plant-based life support systems. Moreover, the basic reproductive biological problems of aquatic animal breeding under reduced gravity are explained leading to a disposition of essential research programs in this context.

Space Station Biological Research Project.

PubMed

Johnson, C C; Wade, C E; Givens, J J

1997-06-01

To meet NASA's objective of using the unique aspects of the space environment to expand fundamental knowledge in the biological sciences, the Space Station Biological Research Project at Ames Research Center is developing, or providing oversight, for two major suites of hardware which will be installed on the International Space Station (ISS). The first, the Gravitational Biology Facility, consists of Habitats to support plants, rodents, cells, aquatic specimens, avian and reptilian eggs, and insects and the Habitat Holding Rack in which to house them at microgravity; the second, the Centrifuge Facility, consists of a 2.5 m diameter centrifuge that will provide acceleration levels between 0.01 g and 2.0 g and a Life Sciences Glovebox. These two facilities will support the conduct of experiments to: 1) investigate the effect of microgravity on living systems; 2) what level of gravity is required to maintain normal form and function, and 3) study the use of artificial gravity as a countermeasure to the deleterious effects of microgravity observed in the crew. Upon completion, the ISS will have three complementary laboratory modules provided by NASA, the European Space Agency and the Japanese space agency, NASDA. Use of all facilities in each of the modules will be available to investigators from participating space agencies. With the advent of the ISS, space-based gravitational biology research will transition from 10-16 day short-duration Space Shuttle flights to 90-day-or-longer ISS increments.

Space Station Biological Research Project

NASA Technical Reports Server (NTRS)

Johnson, C. C.; Wade, C. E.; Givens, J. J.

1997-01-01

To meet NASA's objective of using the unique aspects of the space environment to expand fundamental knowledge in the biological sciences, the Space Station Biological Research Project at Ames Research Center is developing, or providing oversight, for two major suites of hardware which will be installed on the International Space Station (ISS). The first, the Gravitational Biology Facility, consists of Habitats to support plants, rodents, cells, aquatic specimens, avian and reptilian eggs, and insects and the Habitat Holding Rack in which to house them at microgravity; the second, the Centrifuge Facility, consists of a 2.5 m diameter centrifuge that will provide acceleration levels between 0.01 g and 2.0 g and a Life Sciences Glovebox. These two facilities will support the conduct of experiments to: 1) investigate the effect of microgravity on living systems; 2) what level of gravity is required to maintain normal form and function, and 3) study the use of artificial gravity as a countermeasure to the deleterious effects of microgravity observed in the crew. Upon completion, the ISS will have three complementary laboratory modules provided by NASA, the European Space Agency and the Japanese space agency, NASDA. Use of all facilities in each of the modules will be available to investigators from participating space agencies. With the advent of the ISS, space-based gravitational biology research will transition from 10-16 day short-duration Space Shuttle flights to 90-day-or-longer ISS increments.

Kits in Motion

ERIC Educational Resources Information Center

Gee, Maureen

1975-01-01

Discusses three kits developed by museums in British Columbia for use in rural classrooms. The science kit on marine biology consists of modules which included specimens, books, audiovisual materials and student activities. (BR)

Low Fidelity Imitation of Atypical Biological Kinematics in Autism Spectrum Disorders Is Modulated by Self-Generated Selective Attention

ERIC Educational Resources Information Center

Hayes, Spencer J.; Andrew, Matthew; Elliott, Digby; Gowen, Emma; Bennett, Simon J.

2016-01-01

We examined whether adults with autism had difficulty imitating atypical biological kinematics. To reduce the impact that higher-order processes have on imitation we used a non-human agent model to control social attention, and removed end-state target goals in half of the trials to minimise goal-directed attention. Findings showed that only…

Comparative Proteomics of Tandem Mass Spectrometry Analyses for Bacterial Strains Identification and Differentiation

DTIC Science & Technology

2012-02-01

risk, bio -terrorism utility, Homeland Security, agricultural monitoring, quality of foodstuffs, environmental monitoring, and biological warfare agents...CAL19717 Putative surface antigen CAL21872 Putative sigma 54 modulation protein NP_395233 Plasminogen activator protease precursor CAL19882 OMP...S. (2005). Chemical and biological weapons : current concepts for future defenses. Johns Hopkins APL Tech. Digest, 26, 321-333. Dworzanski, J.P

Techniques and instrumental complex for research of influence of microwaves encoded by brain neural signals on biological objects’ psycho physiological state

NASA Astrophysics Data System (ADS)

Gurkovskiy, B. V.; Zhuravlev, B. V.; Onishchenko, E. M.; Simakov, A. B.; Trifonova, N. Yu; Voronov, Yu A.

2016-10-01

New instrumental technique for research of the psycho-physiological reactions of the bio-objects under the microwave electromagnetic radiation, modulated by interval patterns of neural activity in the brain registered under different biological motivations, are suggested. The preliminary results of these new tool tests in real psycho physiological experiments on rats are presented.

Inorganic hydrogen polysulfides: chemistry, chemical biology and detection.

PubMed

Liu, Heng; Radford, Miles N; Yang, Chun-Tao; Chen, Wei; Xian, Ming

2018-04-18

Recent studies suggest that inorganic hydrogen polysulfides (H 2 S n , n ≥ 2) play important regulatory roles in redox biology. Modulation of their cellular levels could have potential therapeutic value. This review article focuses on our current understanding of the biosynthesis, biofunctions, fundamental physical/chemical properties, detection methods and delivery techniques of H 2 S n . © 2018 The British Pharmacological Society.

Optical Techniques for the Remote Detection of Biological Aerosols

DTIC Science & Technology

1974-08-01

1) Laboratory exneriments (2) Remote detection experiments. In the first phase , the optical characteristics of several selected biological...the-art optical sensor system. The estimates were favorable, and a second research phase was initiated. Remote detection experiments were conducted...that of phase fluorometry. The fluorescence is excited by 3. continuous light source, the output of which is modulated at a high freeuency by an optical

Hepcidin modulation in human diseases: From research to clinic

PubMed Central

Piperno, Alberto; Mariani, Raffaella; Trombini, Paola; Girelli, Domenico

2009-01-01

By modulating hepcidin production, an organism controls intestinal iron absorption, iron uptake and mobilization from stores to meet body iron need. In recent years there has been important advancement in our knowledge of hepcidin regulation that also has implications for understanding the physiopathology of some human disorders. Since the discovery of hepcidin and the demonstration of its pivotal role in iron homeostasis, there has been a substantial interest in developing a reliable assay of the hormone in biological fluids. Measurement of hepcidin in biological fluids can improve our understanding of iron diseases and be a useful tool for diagnosis and clinical management of these disorders. We reviewed the literature and our own research on hepcidin to give an updated status of the situation in this rapidly evolving field. PMID:19195055

Identification of Modules in Protein-Protein Interaction Networks

NASA Astrophysics Data System (ADS)

Erten, Sinan; Koyutürk, Mehmet

In biological systems, most processes are carried out through orchestration of multiple interacting molecules. These interactions are often abstracted using network models. A key feature of cellular networks is their modularity, which contributes significantly to the robustness, as well as adaptability of biological systems. Therefore, modularization of cellular networks is likely to be useful in obtaining insights into the working principles of cellular systems, as well as building tractable models of cellular organization and dynamics. A common, high-throughput source of data on molecular interactions is in the form of physical interactions between proteins, which are organized into protein-protein interaction (PPI) networks. This chapter provides an overview on identification and analysis of functional modules in PPI networks, which has been an active area of research in the last decade.

Wound healing process and mediators: Implications for modulations for hernia repair and mesh integration.

PubMed

Sadava, Emmanuel E; Krpata, David M; Gao, Yue; Rosen, Michael J; Novitsky, Yuri W

2014-01-01

In recent years, major advances have been accomplished in abdominal wall reconstruction. Introduction of newer prostheses have improved outcomes, but elimination of mesh-related morbidity is still an elusive issue. It is believed that host foreign body reaction to prosthesis plays an important role in the biology of these complications, so understanding of the molecular mechanisms behind mesh-tissue interactions may be a key for upcoming therapies. It appears that increasing biocompatibility of both synthetic prosthesis and biologic scaffolds might be the main avenues to achieve better outcomes. This manuscript provides an overview of major effectors of wound healing with particular emphasis on how their modulation might improve outcomes in tissue remodeling and mesh integration. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

The modulating impact of illumination and background radiation on 8 Hz-induced infrasound effect on physicochemical properties of physiolagical solution.

PubMed

Baghdasaryan, Naira; Mikayelyan, Yerazik; Barseghyan, Sedrak; Dadasyan, Erna; Ayrapetyan, Sinerik

2012-12-01

At present, when the level of background ionizing radiation is increasing in a number of world locations, the problem of the study of biological effect of high background radiation becomes one of the extremely important global problems in modern life sciences. The modern research in biophysics proved that water is a most essential target, through which the biological effects of ionizing and non-ionizing radiations are realized. Therefore, there is no doubt about the strong dependency of non-ionizing radiation-induced effect on the level of background radiation. Findings have shown that illumination and background radiation have a strong modulation effect on infrasound-induced impacts on water physicochemical properties, which could also have appropriate effect on living organisms.

Reclamation of the wastewater from an industrial park using hollow-fibre and spiral-wound membranes: 50 m3 d(-1) pilot testing and cost evaluation.

PubMed

Chu, C P; Jiaoa, S R; Hung, J M; Lu, C J; Chung, Y J

2009-08-01

The feasibility of reclaiming effluent from industrial park wastewater treatment plants through a membrane process was evaluated in three phases. In phase 1 we selected nine wastewater treatment plants (WWTPs), each with a design capacity exceeding 10,000 m3 d(-1), and analyzed the corresponding effluent composition. 'Potential recycling percentage', R, ranged from 50% to 80% for the industrial park WWTPs, indicating a high feasibility for the reuse of effluent. In phase 2, a 50 m3 d(-1) pilot plant was installed in one of the selected WWTPs and underwent testing for one year. The quality of the reclaimed water was suitable for general-purpose industrial use. In the two ultrafiltration (UF) modules tested, the hydrophilic polyethersulfone hollow-fibre module was more tolerant to variable properties, and had higher recycling percentages than those of backwashable hydrophobic polyvinylidene difluoride spiral-wound module. Using the spiral-wound UF module helped reduce the cost for producing 1 m3 of reclaimed water (US$0.80) compared with a hollow-fibre module (US$0.88). In phase 3, we evaluated the negative effects of refluxing the reverse osmosis retentate, containing high total dissolved solids and non-biodegradable organics, with the biological treatment unit of the upstream WWTP. Biological compactibility tests showed that the refluxed retentate ratio should be reduced to maintain the conductivity of mixed liquor in the aeration tank at less than 110% of the original value.

Correlation transfer and diffusion of ultrasound-modulated multiply scattered light.

PubMed

Sakadzić, Sava; Wang, Lihong V

2006-04-28

We develop a temporal correlation transfer equation (CTE) and a temporal correlation diffusion equation (CDE) for ultrasound-modulated multiply scattered light. These equations can be applied to an optically scattering medium with embedded optically scattering and absorbing objects to calculate the power spectrum of light modulated by a nonuniform ultrasound field. We present an analytical solution based on the CDE and Monte Carlo simulation results for light modulated by a cylinder of ultrasound in an optically scattering slab. We further validate with experimental measurements the numerical calculations for an actual ultrasound field. The CTE and CDE are valid for moderate ultrasound pressures and on a length scale comparable with the optical transport mean-free path. These equations should be applicable to a wide spectrum of conditions for ultrasound-modulated optical tomography of soft biological tissues.

Robots Make Intelligent Teachers

ERIC Educational Resources Information Center

Trotter, Robert J.

1973-01-01

Discussion of the use of teaching machines to help a child learn the basics of geometry. Fully developed educational modules for such subjects as physics, biology, physiology and linguistics are forth-coming. (EB)

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.

Image processing and recognition for biological images

PubMed Central

Uchida, Seiichi

2013-01-01

This paper reviews image processing and pattern recognition techniques, which will be useful to analyze bioimages. Although this paper does not provide their technical details, it will be possible to grasp their main tasks and typical tools to handle the tasks. Image processing is a large research area to improve the visibility of an input image and acquire some valuable information from it. As the main tasks of image processing, this paper introduces gray-level transformation, binarization, image filtering, image segmentation, visual object tracking, optical flow and image registration. Image pattern recognition is the technique to classify an input image into one of the predefined classes and also has a large research area. This paper overviews its two main modules, that is, feature extraction module and classification module. Throughout the paper, it will be emphasized that bioimage is a very difficult target for even state-of-the-art image processing and pattern recognition techniques due to noises, deformations, etc. This paper is expected to be one tutorial guide to bridge biology and image processing researchers for their further collaboration to tackle such a difficult target. PMID:23560739

Eicosanoids: an emerging role in dendritic cell biology.

PubMed

Harizi, Hedi; Gualde, Norbert

2004-01-01

The arachidonic acid (AA)-derived metabolites, termed eicosanoids, are potent lipid mediators with a key role in immune and inflammatory responses. In the immune system, eicosanoids such as prostaglandins (PGs) and leukotrienes (LTs) are produced predominately by antigen-presenting cells (APC), including macrophages and dendritic cells (DC). DC constitute a family of bone marrow-derived professional APC that play a critical role in the induction and modulation of both innate and adaptive immunity. For many years, macrophages were considered as major producers of eicosanoids that are thought to drastically affect their function. Studies concerning the modulation of DC biology by eicosanoids show that PGs and LTs have the potential to affect the maturation, cytokine-producing capacity, Th cell-polarizing ability, and migration of DC. In addition, the development of DC from bone marrow progenitors appears to be under the control of some eicosanoids. Understanding the actions of eicosanoids and their receptors on APC functions is crucial for the generation of efficient DC for therapeutic purposes in patients. In this review, we summarize the current understanding of how DC functions are modulated by eicosanoids.

Insights into TREM2 biology by network analysis of human brain gene expression data

PubMed Central

Forabosco, Paola; Ramasamy, Adaikalavan; Trabzuni, Daniah; Walker, Robert; Smith, Colin; Bras, Jose; Levine, Adam P.; Hardy, John; Pocock, Jennifer M.; Guerreiro, Rita; Weale, Michael E.; Ryten, Mina

2013-01-01

Rare variants in TREM2 cause susceptibility to late-onset Alzheimer's disease. Here we use microarray-based expression data generated from 101 neuropathologically normal individuals and covering 10 brain regions, including the hippocampus, to understand TREM2 biology in human brain. Using network analysis, we detect a highly preserved TREM2-containing module in human brain, show that it relates to microglia, and demonstrate that TREM2 is a hub gene in 5 brain regions, including the hippocampus, suggesting that it can drive module function. Using enrichment analysis we show significant overrepresentation of genes implicated in the adaptive and innate immune system. Inspection of genes with the highest connectivity to TREM2 suggests that it plays a key role in mediating changes in the microglial cytoskeleton necessary not only for phagocytosis, but also migration. Most importantly, we show that the TREM2-containing module is significantly enriched for genes genetically implicated in Alzheimer's disease, multiple sclerosis, and motor neuron disease, implying that these diseases share common pathways centered on microglia and that among the genes identified are possible new disease-relevant genes. PMID:23855984

Design of selective nuclear receptor modulators: RAR and RXR as a case study.

PubMed

de Lera, Angel R; Bourguet, William; Altucci, Lucia; Gronemeyer, Hinrich

2007-10-01

Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are members of the nuclear receptor superfamily whose effects on cell growth and survival can be modulated therapeutically by small-molecule ligands. Although compounds that target these receptors are powerful anticancer drugs, their use is limited by toxicity. An improved understanding of the structural biology of RXRs and RARs and recent advances in the chemical synthesis of modified retinoid and rexinoid ligands should enable the rational design of more selective agents that might overcome such problems. Here, we review structural data for RXRs and RARs, discuss strategies in the design of selective RXR and RAR modulators, and consider lessons that can be learned for the design of selective nuclear-receptor modulators in general.

Modulation of DNA binding by gene-specific transcription factors.

PubMed

Schleif, Robert F

2013-10-01

The transcription of many genes, particularly in prokaryotes, is controlled by transcription factors whose activity can be modulated by controlling their DNA binding affinity. Understanding the molecular mechanisms by which DNA binding affinity is regulated is important, but because forming definitive conclusions usually requires detailed structural information in combination with data from extensive biophysical, biochemical, and sometimes genetic experiments, little is truly understood about this topic. This review describes the biological requirements placed upon DNA binding transcription factors and their consequent properties, particularly the ways that DNA binding affinity can be modulated and methods for its study. What is known and not known about the mechanisms modulating the DNA binding affinity of a number of prokaryotic transcription factors, including CAP and lac repressor, is provided.

Focusing light through scattering media by polarization modulation based generalized digital optical phase conjugation

NASA Astrophysics Data System (ADS)

Yang, Jiamiao; Shen, Yuecheng; Liu, Yan; Hemphill, Ashton S.; Wang, Lihong V.

2017-11-01

Optical scattering prevents light from being focused through thick biological tissue at depths greater than ˜1 mm. To break this optical diffusion limit, digital optical phase conjugation (DOPC) based wavefront shaping techniques are being actively developed. Previous DOPC systems employed spatial light modulators that modulated either the phase or the amplitude of the conjugate light field. Here, we achieve optical focusing through scattering media by using polarization modulation based generalized DOPC. First, we describe an algorithm to extract the polarization map from the measured scattered field. Then, we validate the algorithm through numerical simulations and find that the focusing contrast achieved by polarization modulation is similar to that achieved by phase modulation. Finally, we build a system using an inexpensive twisted nematic liquid crystal based spatial light modulator (SLM) and experimentally demonstrate light focusing through 3-mm thick chicken breast tissue. Since the polarization modulation based SLMs are widely used in displays and are having more and more pixel counts with the prevalence of 4 K displays, these SLMs are inexpensive and valuable devices for wavefront shaping.

Signed weighted gene co-expression network analysis of transcriptional regulation in murine embryonic stem cells

PubMed Central

Mason, Mike J; Fan, Guoping; Plath, Kathrin; Zhou, Qing; Horvath, Steve

2009-01-01

Background Recent work has revealed that a core group of transcription factors (TFs) regulates the key characteristics of embryonic stem (ES) cells: pluripotency and self-renewal. Current efforts focus on identifying genes that play important roles in maintaining pluripotency and self-renewal in ES cells and aim to understand the interactions among these genes. To that end, we investigated the use of unsigned and signed network analysis to identify pluripotency and differentiation related genes. Results We show that signed networks provide a better systems level understanding of the regulatory mechanisms of ES cells than unsigned networks, using two independent murine ES cell expression data sets. Specifically, using signed weighted gene co-expression network analysis (WGCNA), we found a pluripotency module and a differentiation module, which are not identified in unsigned networks. We confirmed the importance of these modules by incorporating genome-wide TF binding data for key ES cell regulators. Interestingly, we find that the pluripotency module is enriched with genes related to DNA damage repair and mitochondrial function in addition to transcriptional regulation. Using a connectivity measure of module membership, we not only identify known regulators of ES cells but also show that Mrpl15, Msh6, Nrf1, Nup133, Ppif, Rbpj, Sh3gl2, and Zfp39, among other genes, have important roles in maintaining ES cell pluripotency and self-renewal. We also report highly significant relationships between module membership and epigenetic modifications (histone modifications and promoter CpG methylation status), which are known to play a role in controlling gene expression during ES cell self-renewal and differentiation. Conclusion Our systems biologic re-analysis of gene expression, transcription factor binding, epigenetic and gene ontology data provides a novel integrative view of ES cell biology. PMID:19619308

Exploring biological interaction networks with tailored weighted quasi-bicliques

PubMed Central

2012-01-01

Background Biological networks provide fundamental insights into the functional characterization of genes and their products, the characterization of DNA-protein interactions, the identification of regulatory mechanisms, and other biological tasks. Due to the experimental and biological complexity, their computational exploitation faces many algorithmic challenges. Results We introduce novel weighted quasi-biclique problems to identify functional modules in biological networks when represented by bipartite graphs. In difference to previous quasi-biclique problems, we include biological interaction levels by using edge-weighted quasi-bicliques. While we prove that our problems are NP-hard, we also describe IP formulations to compute exact solutions for moderately sized networks. Conclusions We verify the effectiveness of our IP solutions using both simulation and empirical data. The simulation shows high quasi-biclique recall rates, and the empirical data corroborate the abilities of our weighted quasi-bicliques in extracting features and recovering missing interactions from biological networks. PMID:22759421

Biological Applications of FM-AFM in Liquid Environment

NASA Astrophysics Data System (ADS)

Fukuma, Takeshi; Jarvis, Suzanne P.

Atomic force microscopy (AFM) was noted for its potential to study biological materials shortly after its first development in 1986 due to its ability to image insulators in liquid environments. The subsequent application of AFM to biology has included lateral characterization via imaging, unraveling of molecules under a tensile load and application of a force either to measure mechanical properties under the tip or to instigate a biochemical response in living cells. To date, the application of frequency modulation AFM (FM-AFM) specifically to biological materials has been limited to relatively few research groups when compared to the extensive application of AFM to biological materials. This is probably due to the perceived complexity of the technique both by researchers in the life sciences and those manufacturing liquid AFMs for biological research. In this chapter, we aim to highlight the advantages of applying the technique to biological materials.

Computer-aided design of biological circuits using TinkerCell.

PubMed

Chandran, Deepak; Bergmann, Frank T; Sauro, Herbert M

2010-01-01

Synthetic biology is an engineering discipline that builds on modeling practices from systems biology and wet-lab techniques from genetic engineering. As synthetic biology advances, efficient procedures will be developed that will allow a synthetic biologist to design, analyze, and build biological networks. In this idealized pipeline, computer-aided design (CAD) is a necessary component. The role of a CAD application would be to allow efficient transition from a general design to a final product. TinkerCell is a design tool for serving this purpose in synthetic biology. In TinkerCell, users build biological networks using biological parts and modules. The network can be analyzed using one of several functions provided by TinkerCell or custom programs from third-party sources. Since best practices for modeling and constructing synthetic biology networks have not yet been established, TinkerCell is designed as a flexible and extensible application that can adjust itself to changes in the field. © 2010 Landes Bioscience

Molecular and physiological manifestations and measurement of aging in humans.

PubMed

Khan, Sadiya S; Singer, Benjamin D; Vaughan, Douglas E

2017-08-01

Biological aging is associated with a reduction in the reparative and regenerative potential in tissues and organs. This reduction manifests as a decreased physiological reserve in response to stress (termed homeostenosis) and a time-dependent failure of complex molecular mechanisms that cumulatively create disorder. Aging inevitably occurs with time in all organisms and emerges on a molecular, cellular, organ, and organismal level with genetic, epigenetic, and environmental modulators. Individuals with the same chronological age exhibit differential trajectories of age-related decline, and it follows that we should assess biological age distinctly from chronological age. In this review, we outline mechanisms of aging with attention to well-described molecular and cellular hallmarks and discuss physiological changes of aging at the organ-system level. We suggest methods to measure aging with attention to both molecular biology (e.g., telomere length and epigenetic marks) and physiological function (e.g., lung function and echocardiographic measurements). Finally, we propose a framework to integrate these molecular and physiological data into a composite score that measures biological aging in humans. Understanding the molecular and physiological phenomena that drive the complex and multifactorial processes underlying the variable pace of biological aging in humans will inform how researchers assess and investigate health and disease over the life course. This composite biological age score could be of use to researchers seeking to characterize normal, accelerated, and exceptionally successful aging as well as to assess the effect of interventions aimed at modulating human aging. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Apollo-Soyuz pamphlet no. 9: General science. [experimental design in Astronomy, Biology, Geophysics, Aeronomy and Materials science

NASA Technical Reports Server (NTRS)

Page, L. W.; From, T. P.

1977-01-01

The objectives and planning activities for the Apollo-Soyuz mission are summarized. Aspects of the space flight considered include the docking module and launch configurations, spacecraft orbits, and weightlessness. The 28 NASA experiments conducted onboard the spacecraft are summarized. The contributions of the mission to the fields of astronomy, geoscience, biology, and materials sciences resulting from the experiments are explored.

Biological Features of the Soil: Advanced Crop and Soil Science. A Course of Study.

ERIC Educational Resources Information Center

Miller, Larry E.

The course of study represents the third of six modules in advanced crop and soil science and introduces the agriculture student to biological features of soil. Upon completing the two day lesson, the student will: (1) realize the vast amount of life present in the soil, (2) be able to list representative animal and plant life in the soil by size,…

Molecular Mechanics and Dynamics Characterization of an "in silico" Mutated Protein: A Stand-Alone Lab Module or Support Activity for "in vivo" and "in vitro" Analyses of Targeted Proteins

ERIC Educational Resources Information Center

Chiang, Harry; Robinson, Lucy C.; Brame, Cynthia J.; Messina, Troy C.

2013-01-01

Over the past 20 years, the biological sciences have increasingly incorporated chemistry, physics, computer science, and mathematics to aid in the development and use of mathematical models. Such combined approaches have been used to address problems from protein structure-function relationships to the workings of complex biological systems.…

Metal-free bioconjugation reactions.

PubMed

van Berkel, Sander S; van Delft, Floris L

2013-01-01

The recent strategy to apply chemical reactions to address fundamental biological questions has led to the emergence of entirely new conjugation reactions that are fast and irreversible, yet so mild and selective that they can be performed even in living cells or organisms. These so-called bioorthogonal reactions open novel avenues, not only in chemical biology research, but also in many other life sciences applications, including the modulation of biopharmaceuticals by site-specific modification approaches.

[Study Plan 2016 of the licentiate of medical surgery of the faculty of higher studies iztacala].

PubMed

Méndez-Cruz, Adolfo René; Novales-Castro, Xavier de Jesús; Ramírez-García, Lilia Isabel; Camarena-Ocampo, Eugenio; Reyes-Reali, Julia; Calderón-Abundes, Uriel; Amato, Dante

2017-01-01

The 2016 undergraduate medical degree curriculum at the Facultad de Estudios Superiores Iztacala of the Universidad Nacional Autónoma de México (UNAM) is presented. It is the result of a long institutional reflection and academic dialog process of approximately three years, which culminated in its approval by UNAM's Academic Council for the Biology, Chemistry, and Health Sciences areas on January 25, 2016. Its most relevant characteristics are: modular organization, four knowledge areas (biomedical, methodological, socio-psychological, and humanistic and medical practice), and new modules such as Seminar of socio-psycho-biological integration; Genetics and molecular biology; Biochemistry and cellular biology; Pharmacological basis of therapeutics; Infectious diseases, microbiology and parasitology; Medical ethics; Public health; and Evidence-based medicine - clinical epidemiology. To achieve a more flexible curriculum, optional modules were included. To make possible the curricular change, improving the teaching strategies, innovating the learning assessment methods, supporting the training and updating of the teaching staff, and establishing a curriculum development committee for following up and evaluating the program, are necessary. Curricular changes are difficult and complex processes; they suppose challenges and opportunities. It is mandatory to plan them carefully and sensitively to allow a successful transition and avoid conflicts for the students, the teachers and the institution.

ePlant and the 3D data display initiative: integrative systems biology on the world wide web.

PubMed

Fucile, Geoffrey; Di Biase, David; Nahal, Hardeep; La, Garon; Khodabandeh, Shokoufeh; Chen, Yani; Easley, Kante; Christendat, Dinesh; Kelley, Lawrence; Provart, Nicholas J

2011-01-10

Visualization tools for biological data are often limited in their ability to interactively integrate data at multiple scales. These computational tools are also typically limited by two-dimensional displays and programmatic implementations that require separate configurations for each of the user's computing devices and recompilation for functional expansion. Towards overcoming these limitations we have developed "ePlant" (http://bar.utoronto.ca/eplant) - a suite of open-source world wide web-based tools for the visualization of large-scale data sets from the model organism Arabidopsis thaliana. These tools display data spanning multiple biological scales on interactive three-dimensional models. Currently, ePlant consists of the following modules: a sequence conservation explorer that includes homology relationships and single nucleotide polymorphism data, a protein structure model explorer, a molecular interaction network explorer, a gene product subcellular localization explorer, and a gene expression pattern explorer. The ePlant's protein structure explorer module represents experimentally determined and theoretical structures covering >70% of the Arabidopsis proteome. The ePlant framework is accessed entirely through a web browser, and is therefore platform-independent. It can be applied to any model organism. To facilitate the development of three-dimensional displays of biological data on the world wide web we have established the "3D Data Display Initiative" (http://3ddi.org).

From "Cellular" RNA to "Smart" RNA: Multiple Roles of RNA in Genome Stability and Beyond.

PubMed

Michelini, Flavia; Jalihal, Ameya P; Francia, Sofia; Meers, Chance; Neeb, Zachary T; Rossiello, Francesca; Gioia, Ubaldo; Aguado, Julio; Jones-Weinert, Corey; Luke, Brian; Biamonti, Giuseppe; Nowacki, Mariusz; Storici, Francesca; Carninci, Piero; Walter, Nils G; Fagagna, Fabrizio d'Adda di

2018-04-25

Coding for proteins has been considered the main function of RNA since the "central dogma" of biology was proposed. The discovery of noncoding transcripts shed light on additional roles of RNA, ranging from the support of polypeptide synthesis, to the assembly of subnuclear structures, to gene expression modulation. Cellular RNA has therefore been recognized as a central player in often unanticipated biological processes, including genomic stability. This ever-expanding list of functions inspired us to think of RNA as a "smart" phone, which has replaced the older obsolete "cellular" phone. In this review, we summarize the last two decades of advances in research on the interface between RNA biology and genome stability. We start with an account of the emergence of noncoding RNA, and then we discuss the involvement of RNA in DNA damage signaling and repair, telomere maintenance, and genomic rearrangements. We continue with the depiction of single-molecule RNA detection techniques, and we conclude by illustrating the possibilities of RNA modulation in hopes of creating or improving new therapies. The widespread biological functions of RNA have made this molecule a reoccurring theme in basic and translational research, warranting it the transcendence from classically studied "cellular" RNA to "smart" RNA.

Improvements in algal lipid production: a systems biology and gene editing approach.

PubMed

Banerjee, Avik; Banerjee, Chiranjib; Negi, Sangeeta; Chang, Jo-Shu; Shukla, Pratyoosh

2018-05-01

In the wake of rising energy demands, microalgae have emerged as potential sources of sustainable and renewable carbon-neutral fuels, such as bio-hydrogen and bio-oil. For rational metabolic engineering, the elucidation of metabolic pathways in fine detail and their manipulation according to requirements is the key to exploiting the use of microalgae. Emergence of site-specific nucleases have revolutionized applied research leading to biotechnological gains. Genome engineering as well as modulation of the endogenous genome with high precision using CRISPR systems is being gradually employed in microalgal research. Further, to optimize and produce better algal platforms, use of systems biology network analysis and integration of omics data is required. This review discusses two important approaches: systems biology and gene editing strategies used on microalgal systems with a focus on biofuel production and sustainable solutions. It also emphasizes that the integration of such systems would contribute and compliment applied research on microalgae. Recent advances in microalgae are discussed, including systems biology, gene editing approaches in lipid bio-synthesis, and antenna engineering. Lastly, it has been attempted here to showcase how CRISPR/Cas systems are a better editing tool than existing techniques that can be utilized for gene modulation and engineering during biofuel production.

Novel Transcriptional Activities of Vitamin E: Inhibition of Cholesterol Biosynthesis

PubMed Central

Valastyan, Scott; Thakur, Varsha; Johnson, Amy; Kumar, Karan; Manor, Danny

2008-01-01

Vitamin E is a dietary lipid that is essential for vertebrate health and fertility. The biological activity of vitamin E is thought to reflect its ability to quench oxygen- and carbon- based free radicals, and thus to protect the organism from oxidative damage. However, recent reports suggest that vitamin E may also display other biological activities. Here, to examine possible mechanisms that may underlie such non-classical activities of vitamin E, we investigated the possibility that it functions as a specific modulator of gene expression. We show that treatment of cultured hepatocytes with RRR-α-tocopherol alters the expression of multiple genes and that these effects are distinct from those elicited by another antioxidant. Genes modulated by vitamin E include those that encode key enzymes in the cholesterol biosynthetic pathway. Correspondingly, vitamin E caused a pronounced inhibition of de novo cholesterol biosynthesis. The transcriptional activities of vitamin E were mediated by attenuating the post-translational processing of the transcription factor SREBP-2 that, in turn, led to a decreased transcriptional activity of sterol responsive elements in the promoters of target genes. These observations indicate that vitamin E possesses novel transcriptional activities that affect fundamental biological processes. Cross talk between tocopherol levels and cholesterol status may be an important facet of the biological activities of vitamin E. PMID:18095660

Impact of constitutional copy number variants on biological pathway evolution.

PubMed

Poptsova, Maria; Banerjee, Samprit; Gokcumen, Omer; Rubin, Mark A; Demichelis, Francesca

2013-01-23

Inherited Copy Number Variants (CNVs) can modulate the expression levels of individual genes. However, little is known about how CNVs alter biological pathways and how this varies across different populations. To trace potential evolutionary changes of well-described biological pathways, we jointly queried the genomes and the transcriptomes of a collection of individuals with Caucasian, Asian or Yoruban descent combining high-resolution array and sequencing data. We implemented an enrichment analysis of pathways accounting for CNVs and genes sizes and detected significant enrichment not only in signal transduction and extracellular biological processes, but also in metabolism pathways. Upon the estimation of CNV population differentiation (CNVs with different polymorphism frequencies across populations), we evaluated that 22% of the pathways contain at least one gene that is proximal to a CNV (CNV-gene pair) that shows significant population differentiation. The majority of these CNV-gene pairs belong to signal transduction pathways and 6% of the CNV-gene pairs show statistical association between the copy number states and the transcript levels. The analysis suggested possible examples of positive selection within individual populations including NF-kB, MAPK signaling pathways, and Alu/L1 retrotransposition factors. Altogether, our results suggest that constitutional CNVs may modulate subtle pathway changes through specific pathway enzymes, which may become fixed in some populations.

Impact of constitutional copy number variants on biological pathway evolution

PubMed Central

2013-01-01

Background Inherited Copy Number Variants (CNVs) can modulate the expression levels of individual genes. However, little is known about how CNVs alter biological pathways and how this varies across different populations. To trace potential evolutionary changes of well-described biological pathways, we jointly queried the genomes and the transcriptomes of a collection of individuals with Caucasian, Asian or Yoruban descent combining high-resolution array and sequencing data. Results We implemented an enrichment analysis of pathways accounting for CNVs and genes sizes and detected significant enrichment not only in signal transduction and extracellular biological processes, but also in metabolism pathways. Upon the estimation of CNV population differentiation (CNVs with different polymorphism frequencies across populations), we evaluated that 22% of the pathways contain at least one gene that is proximal to a CNV (CNV-gene pair) that shows significant population differentiation. The majority of these CNV-gene pairs belong to signal transduction pathways and 6% of the CNV-gene pairs show statistical association between the copy number states and the transcript levels. Conclusions The analysis suggested possible examples of positive selection within individual populations including NF-kB, MAPK signaling pathways, and Alu/L1 retrotransposition factors. Altogether, our results suggest that constitutional CNVs may modulate subtle pathway changes through specific pathway enzymes, which may become fixed in some populations. PMID:23342974

Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks

PubMed Central

Xu, Jianfeng; Lan, Yueheng

2015-01-01

Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks. PMID:25951347

LRP5 regulates human body fat distribution by modulating adipose progenitor biology in a dose- and depot-specific fashion.

PubMed

Loh, Nellie Y; Neville, Matt J; Marinou, Kyriakoula; Hardcastle, Sarah A; Fielding, Barbara A; Duncan, Emma L; McCarthy, Mark I; Tobias, Jonathan H; Gregson, Celia L; Karpe, Fredrik; Christodoulides, Constantinos

2015-02-03

Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired β-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/β-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

LRP5 Regulates Human Body Fat Distribution by Modulating Adipose Progenitor Biology in a Dose- and Depot-Specific Fashion

PubMed Central

Loh, Nellie Y.; Neville, Matt J.; Marinou, Kyriakoula; Hardcastle, Sarah A.; Fielding, Barbara A.; Duncan, Emma L.; McCarthy, Mark I.; Tobias, Jonathan H.; Gregson, Celia L.; Karpe, Fredrik; Christodoulides, Constantinos

2015-01-01

Summary Common variants in WNT pathway genes have been associated with bone mass and fat distribution, the latter predicting diabetes and cardiovascular disease risk. Rare mutations in the WNT co-receptors LRP5 and LRP6 are similarly associated with bone and cardiometabolic disorders. We investigated the role of LRP5 in human adipose tissue. Subjects with gain-of-function LRP5 mutations and high bone mass had enhanced lower-body fat accumulation. Reciprocally, a low bone mineral density-associated common LRP5 allele correlated with increased abdominal adiposity. Ex vivo LRP5 expression was higher in abdominal versus gluteal adipocyte progenitors. Equivalent knockdown of LRP5 in both progenitor types dose-dependently impaired β-catenin signaling and led to distinct biological outcomes: diminished gluteal and enhanced abdominal adipogenesis. These data highlight how depot differences in WNT/β-catenin pathway activity modulate human fat distribution via effects on adipocyte progenitor biology. They also identify LRP5 as a potential pharmacologic target for the treatment of cardiometabolic disorders. PMID:25651180

Evidence for dynamically organized modularity in the yeast protein-protein interaction network

NASA Astrophysics Data System (ADS)

Han, Jing-Dong J.; Bertin, Nicolas; Hao, Tong; Goldberg, Debra S.; Berriz, Gabriel F.; Zhang, Lan V.; Dupuy, Denis; Walhout, Albertha J. M.; Cusick, Michael E.; Roth, Frederick P.; Vidal, Marc

2004-07-01

In apparently scale-free protein-protein interaction networks, or `interactome' networks, most proteins interact with few partners, whereas a small but significant proportion of proteins, the `hubs', interact with many partners. Both biological and non-biological scale-free networks are particularly resistant to random node removal but are extremely sensitive to the targeted removal of hubs. A link between the potential scale-free topology of interactome networks and genetic robustness seems to exist, because knockouts of yeast genes encoding hubs are approximately threefold more likely to confer lethality than those of non-hubs. Here we investigate how hubs might contribute to robustness and other cellular properties for protein-protein interactions dynamically regulated both in time and in space. We uncovered two types of hub: `party' hubs, which interact with most of their partners simultaneously, and `date' hubs, which bind their different partners at different times or locations. Both in silico studies of network connectivity and genetic interactions described in vivo support a model of organized modularity in which date hubs organize the proteome, connecting biological processes-or modules -to each other, whereas party hubs function inside modules.

Multidisciplinary approaches to solar hydrogen

PubMed Central

Bren, Kara L.

2015-01-01

This review summarizes three different approaches to engineering systems for the solar-driven evolution of hydrogen fuel from water: molecular, nanomaterials and biomolecular. Molecular systems have the advantage of being highly amenable to modification and detailed study and have provided great insight into photophysics, electron transfer and catalytic mechanism. However, they tend to display poor stability. Systems based on nanomaterials are more robust but also are more difficult to synthesize in a controlled manner and to modify and study in detail. Biomolecular systems share many properties with molecular systems and have the advantage of displaying inherently high efficiencies for light absorption, electron–hole separation and catalysis. However, biological systems must be engineered to couple modules that capture and convert solar photons to modules that produce hydrogen fuel. Furthermore, biological systems are prone to degradation when employed in vitro. Advances that use combinations of these three tactics also are described. Multidisciplinary approaches to this problem allow scientists to take advantage of the best features of biological, molecular and nanomaterials systems provided that the components can be coupled for efficient function. PMID:26052425

Vertical and horizontal integration of bioinformatics education: A modular, interdisciplinary approach.

PubMed

Furge, Laura Lowe; Stevens-Truss, Regina; Moore, D Blaine; Langeland, James A

2009-01-01

Bioinformatics education for undergraduates has been approached primarily in two ways: introduction of new courses with largely bioinformatics focus or introduction of bioinformatics experiences into existing courses. For small colleges such as Kalamazoo, creation of new courses within an already resource-stretched setting has not been an option. Furthermore, we believe that a true interdisciplinary science experience would be best served by introduction of bioinformatics modules within existing courses in biology and chemistry and other complementary departments. To that end, with support from the Howard Hughes Medical Institute, we have developed over a dozen independent bioinformatics modules for our students that are incorporated into courses ranging from general chemistry and biology, advanced specialty courses, and classes in complementary disciplines such as computer science, mathematics, and physics. These activities have largely promoted active learning in our classrooms and have enhanced student understanding of course materials. Herein, we describe our program, the activities we have developed, and assessment of our endeavors in this area. Copyright © 2009 International Union of Biochemistry and Molecular Biology, Inc.

High Mobility Group N Proteins Modulate the Fidelity of the Cellular Transcriptional Profile in a Tissue- and Variant-specific Manner*

PubMed Central

Kugler, Jamie E.; Horsch, Marion; Huang, Di; Furusawa, Takashi; Rochman, Mark; Garrett, Lillian; Becker, Lore; Bohla, Alexander; Hölter, Sabine M.; Prehn, Cornelia; Rathkolb, Birgit; Racz, Ildikó; Aguilar-Pimentel, Juan Antonio; Adler, Thure; Adamski, Jerzy; Beckers, Johannes; Busch, Dirk H.; Eickelberg, Oliver; Klopstock, Thomas; Ollert, Markus; Stöger, Tobias; Wolf, Eckhard; Wurst, Wolfgang; Yildirim, Ali Önder; Zimmer, Andreas; Gailus-Durner, Valérie; Fuchs, Helmut; Hrabě de Angelis, Martin; Garfinkel, Benny; Orly, Joseph; Ovcharenko, Ivan; Bustin, Michael

2013-01-01

The nuclei of most vertebrate cells contain members of the high mobility group N (HMGN) protein family, which bind specifically to nucleosome core particles and affect chromatin structure and function, including transcription. Here, we study the biological role of this protein family by systematic analysis of phenotypes and tissue transcription profiles in mice lacking functional HMGN variants. Phenotypic analysis of Hmgn1tm1/tm1, Hmgn3tm1/tm1, and Hmgn5tm1/tm1 mice and their wild type littermates with a battery of standardized tests uncovered variant-specific abnormalities. Gene expression analysis of four different tissues in each of the Hmgntm1/tm1 lines reveals very little overlap between genes affected by specific variants in different tissues. Pathway analysis reveals that loss of an HMGN variant subtly affects expression of numerous genes in specific biological processes. We conclude that within the biological framework of an entire organism, HMGNs modulate the fidelity of the cellular transcriptional profile in a tissue- and HMGN variant-specific manner. PMID:23620591

Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases.

PubMed

Louridas, George E; Lourida, Katerina G

2017-02-21

Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

Micro/nanofabricated environments for synthetic biology.

PubMed

Collier, C Patrick; Simpson, Michael L

2011-08-01

A better understanding of how confinement, crowding and reduced dimensionality modulate reactivity and reaction dynamics will aid in the rational and systematic discovery of functionality in complex biological systems. Artificial microfabricated and nanofabricated structures have helped elucidate the effects of nanoscale spatial confinement and segregation on biological behavior, particularly when integrated with microfluidics, through precise control in both space and time of diffusible signals and binding interactions. Examples of nanostructured interfaces for synthetic biology include the development of cell-like compartments for encapsulating biochemical reactions, nanostructured environments for fundamental studies of diffusion, molecular transport and biochemical reaction kinetics, and regulation of biomolecular interactions as functions of microfabricated and nanofabricated topological constraints. Copyright © 2011 Elsevier Ltd. All rights reserved.

Disease networks. Uncovering disease-disease relationships through the incomplete interactome.

PubMed

Menche, Jörg; Sharma, Amitabh; Kitsak, Maksim; Ghiassian, Susan Dina; Vidal, Marc; Loscalzo, Joseph; Barabási, Albert-László

2015-02-20

According to the disease module hypothesis, the cellular components associated with a disease segregate in the same neighborhood of the human interactome, the map of biologically relevant molecular interactions. Yet, given the incompleteness of the interactome and the limited knowledge of disease-associated genes, it is not obvious if the available data have sufficient coverage to map out modules associated with each disease. Here we derive mathematical conditions for the identifiability of disease modules and show that the network-based location of each disease module determines its pathobiological relationship to other diseases. For example, diseases with overlapping network modules show significant coexpression patterns, symptom similarity, and comorbidity, whereas diseases residing in separated network neighborhoods are phenotypically distinct. These tools represent an interactome-based platform to predict molecular commonalities between phenotypically related diseases, even if they do not share primary disease genes. Copyright © 2015, American Association for the Advancement of Science.

Constraints and spandrels of interareal connectomes

PubMed Central

Rubinov, Mikail

2016-01-01

Interareal connectomes are whole-brain wiring diagrams of white-matter pathways. Recent studies have identified modules, hubs, module hierarchies and rich clubs as structural hallmarks of these wiring diagrams. An influential current theory postulates that connectome modules are adequately explained by evolutionary pressures for wiring economy, but that the other hallmarks are not explained by such pressures and are therefore less trivial. Here, we use constraint network models to test these postulates in current gold-standard vertebrate and invertebrate interareal-connectome reconstructions. We show that empirical wiring-cost constraints inadequately explain connectome module organization, and that simultaneous module and hub constraints induce the structural byproducts of hierarchies and rich clubs. These byproducts, known as spandrels in evolutionary biology, include the structural substrate of the default-mode network. Our results imply that currently standard connectome characterizations are based on circular analyses or double dipping, and we emphasize an integrative approach to future connectome analyses for avoiding such pitfalls. PMID:27924867

Constraints and spandrels of interareal connectomes.

PubMed

Rubinov, Mikail

2016-12-07

Interareal connectomes are whole-brain wiring diagrams of white-matter pathways. Recent studies have identified modules, hubs, module hierarchies and rich clubs as structural hallmarks of these wiring diagrams. An influential current theory postulates that connectome modules are adequately explained by evolutionary pressures for wiring economy, but that the other hallmarks are not explained by such pressures and are therefore less trivial. Here, we use constraint network models to test these postulates in current gold-standard vertebrate and invertebrate interareal-connectome reconstructions. We show that empirical wiring-cost constraints inadequately explain connectome module organization, and that simultaneous module and hub constraints induce the structural byproducts of hierarchies and rich clubs. These byproducts, known as spandrels in evolutionary biology, include the structural substrate of the default-mode network. Our results imply that currently standard connectome characterizations are based on circular analyses or double dipping, and we emphasize an integrative approach to future connectome analyses for avoiding such pitfalls.

Two-dimensional nuclear magnetic resonance structure determination module for introductory biochemistry: synthesis and structural characterization of lyso-glycerophospholipids.

PubMed

Garrett, Teresa A; Rose, Rebecca L; Bell, Sidney M

2013-01-01

In this laboratory module, introductory biochemistry students are exposed to two-dimensional (1) H-nuclear magnetic resonance of glycerophospholipids (GPLs). Working in groups of three, students enzymatically synthesized and purified a variety of 2-acyl lyso GPLs. The structure of the 2-acyl lyso GPL was verified using (1) H-correlation spectroscopy. Students scored significantly higher on an assessment of NMR knowledge after having participated in this lab module and in comparison to a similar cohort who did not participate. Inaddition, student confidence in their NMR knowledge and abilities increased 62% following the module and correlated with their ability to apply their NMR knowledge. Based on these results, the laboratory module was very effective at providing students with a more extensive understanding of the underlying concepts of NMR as a tool for structural determination. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

Pigment composition and concentrations within the plant (Ceratophyllum demersum L.) component of the STS-89 C.E.B.A.S. Mini-Module spaceflight experiment

NASA Technical Reports Server (NTRS)

Voeste, D.; Levine, L. H.; Levine, H. G.; Blum, V.; Wheeler, R. M. (Principal Investigator)

2003-01-01

The Closed Equilibrated Biological Aquatic System (C.E.B.A.S.) Mini-Module, a Space Shuttle middeck locker payload which supports a variety of aquatic inhabitants (fish, snails, plants and bacteria) in an enclosed 8.6 L chamber, was tested for its biological stability in microgravity. The aquatic plant, Ceratophyllum demersum L., was critical for the vitality and functioning of this artificial mini-ecosystem. Its photosynthetic pigment concentrations were of interest due to their light harvesting and protective functions. "Post-flight" chlorophyll and carotenoid concentrations within Ceratophyllum apical segments were directly related to the quantities of light received in the experiments, with microgravity exposure (STS-89) failing to account for any significant deviation from ground control studies. Published by Elsevier Science Ltd on behalf of COSPAR.

ENSO Modulations due to Interannual Variability of Freshwater Forcing and Ocean Biology-induced Heating in the Tropical Pacific

PubMed Central

Zhang, Rong-Hua; Gao, Chuan; Kang, Xianbiao; Zhi, Hai; Wang, Zhanggui; Feng, Licheng

2015-01-01

Recent studies have identified clear climate feedbacks associated with interannual variations in freshwater forcing (FWF) and ocean biology-induced heating (OBH) in the tropical Pacific. The interrelationships among the related anomaly fields are analyzed using hybrid coupled model (HCM) simulations to illustrate their combined roles in modulating the El Niño-Southern Oscillation (ENSO). The HCM-based supporting experiments are performed to isolate the related feedbacks, with interannually varying FWF and OBH being represented individually or collectively, which allows their effects to be examined in a clear way. It is demonstrated that the interannual freshwater forcing enhances ENSO variability and slightly prolongs the simulated ENSO period, while the interannual OBH reduces ENSO variability and slightly shortens the ENSO period, with their feedback effects tending to counteract each other. PMID:26678931

The "sweet" side of the protein corona: effects of glycosylation on nanoparticle-cell interactions.

PubMed

Wan, Sha; Kelly, Philip M; Mahon, Eugene; Stöckmann, Henning; Rudd, Pauline M; Caruso, Frank; Dawson, Kenneth A; Yan, Yan; Monopoli, Marco P

2015-02-24

The significance of a protein corona on nanoparticles in modulating particle properties and their biological interactions has been widely acknowledged. The protein corona is derived from proteins in biological fluids, many of which are glycosylated. To date, the glycans on the proteins have been largely overlooked in studies of nanoparticle-cell interactions. In this study, we demonstrate that glycosylation of the protein corona plays an important role in maintaining the colloidal stability of nanoparticles and influences nanoparticle-cell interactions. The removal of glycans from the protein corona enhances cell membrane adhesion and cell uptake of nanoparticles in comparison with the fully glycosylated form, resulting in the generation of a pro-inflammatory milieu by macrophages. This study highlights that the post-translational modification of proteins can significantly impact nanoparticle-cell interactions by modulating the protein corona properties.

Crosstalk between poly(ADP-ribose) polymerase and sirtuin enzymes

PubMed Central

Cantó, Carles; Sauve, Anthony A.; Bai, Peter

2013-01-01

Poly(ADP-ribose) polymerases (PARPs) are NAD+ dependent enzymes that were identified as DNA repair proteins, however, today it seems clear that PARPs are responsible for a plethora of biological functions. Sirtuins (SIRTs) are NAD+-dependent deacetylase enzymes involved in the same biological processes as PARPs raising the question whether PARP and SIRT enzymes may interact with each other in physiological and pathophysiological conditions. Hereby we review the current understanding of the SIRT-PARP interplay in regard to the biochemical nature of the interaction (competition for the common NAD+ substrate, mutual posttranslational modifications and direct transcriptional effects) and the physiological, or pathophysiological consequences of the interactions (metabolic events, oxidative stress response, genomic stability and ageing). Finally, we give an overview of the possibilities of pharmacological intervention to modulate PARP and SIRT enzymes either directly, or through modulating NAD+ homeostasis. PMID:23357756

Nontraditional inheritance: Genetics and the nature of science, now titled, The puzzle of inheritance: Genetics and the methods of science. Final report

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

McInerney, J.D.

1998-08-31

This project led to the development of an instructional module designed for use in high school biology classes. The module contains two major components. The first is an overview for teachers, which introduces the module, describes the Human Genome Project, and addresses issues in the philosophy of science and some of the ethical, legal, and social implications of research in genetics. It provides a survey of fundamental genetics concepts and of new, nontraditional concepts of inheritance. The second component provides six instructional activities appropriate for high school or introductory college students.

Biosphere 2 test module experimentation program

NASA Technical Reports Server (NTRS)

Alling, Abigail; Leigh, Linda S.; Maccallum, Taber; Alvarez-Romo, Norberto

1990-01-01

The Biosphere 2 Test Module is a facility which has the capability to do either short or long term closures: five month closures with plants were conducted. Also conducted were investigations of specific problems, such as trace gas purification by bioregenerative systems by in-putting a fixed concentration of a gas and observing its uptake over time. In other Test Module experiments, the concentration of one gas was changed to observe what effects this has on other gases present or on the system. The science of biospherics which encompasses the study of closed biological systems provides an opening into the future in space as well as in the Earth's biosphere.

Providing Experiential Business and Management Training for Biomedical Research Trainees.

PubMed

Petrie, Kimberly A; Carnahan, Robert H; Brown, Abigail M; Gould, Kathleen L

2017-01-01

Many biomedical PhD trainees lack exposure to business principles, which limits their competitiveness and effectiveness in academic and industry careers. To fill this training gap, we developed Business and Management Principles for Scientists, a semester-long program that combined didactic exposure to business fundamentals with practical team-based projects aimed at solving real business problems encountered by institutional shared--resource core facilities. The program also included a retreat featuring presentations by and networking with local life science entrepreneurs and final team presentations to expert judges. Quantitative and qualitative metrics were used to evaluate the program's impact on trainees. A pretest-posttest approach was used to assess trainees' baseline knowledge and mastery of module concepts, and each individual's pretest and posttest responses were compared. The mean score improved by more than 17 percentage points. Trainees also took an online survey to provide feedback about the module. Nearly all participants agreed or strongly agreed that the module was a valuable use of their time and will help guide their career decisions and that project work helped drive home module concepts. More than 75% of trainees reported discussing the module with their research advisors, and all of these participants reported supportive or neutral responses. Collectively, the trainee feedback about the module, improvement in test scores, and trainee perception of advisor support suggest that this short module is an effective method of providing scientists with efficient and meaningful exposure to business concepts. © 2017 K. A. Petrie et al. CBE—Life Sciences Education © 2017 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).

GoldenBraid 2.0: A Comprehensive DNA Assembly Framework for Plant Synthetic Biology1[C][W][OA

PubMed Central

Sarrion-Perdigones, Alejandro; Vazquez-Vilar, Marta; Palací, Jorge; Castelijns, Bas; Forment, Javier; Ziarsolo, Peio; Blanca, José; Granell, Antonio; Orzaez, Diego

2013-01-01

Plant synthetic biology aims to apply engineering principles to plant genetic design. One strategic requirement of plant synthetic biology is the adoption of common standardized technologies that facilitate the construction of increasingly complex multigene structures at the DNA level while enabling the exchange of genetic building blocks among plant bioengineers. Here, we describe GoldenBraid 2.0 (GB2.0), a comprehensive technological framework that aims to foster the exchange of standard DNA parts for plant synthetic biology. GB2.0 relies on the use of type IIS restriction enzymes for DNA assembly and proposes a modular cloning schema with positional notation that resembles the grammar of natural languages. Apart from providing an optimized cloning strategy that generates fully exchangeable genetic elements for multigene engineering, the GB2.0 toolkit offers an ever-growing open collection of DNA parts, including a group of functionally tested, premade genetic modules to build frequently used modules like constitutive and inducible expression cassettes, endogenous gene silencing and protein-protein interaction tools, etc. Use of the GB2.0 framework is facilitated by a number of Web resources that include a publicly available database, tutorials, and a software package that provides in silico simulations and laboratory protocols for GB2.0 part domestication and multigene engineering. In short, GB2.0 provides a framework to exchange both information and physical DNA elements among bioengineers to help implement plant synthetic biology projects. PMID:23669743

GoldenBraid 2.0: a comprehensive DNA assembly framework for plant synthetic biology.

PubMed

Sarrion-Perdigones, Alejandro; Vazquez-Vilar, Marta; Palací, Jorge; Castelijns, Bas; Forment, Javier; Ziarsolo, Peio; Blanca, José; Granell, Antonio; Orzaez, Diego

2013-07-01

Plant synthetic biology aims to apply engineering principles to plant genetic design. One strategic requirement of plant synthetic biology is the adoption of common standardized technologies that facilitate the construction of increasingly complex multigene structures at the DNA level while enabling the exchange of genetic building blocks among plant bioengineers. Here, we describe GoldenBraid 2.0 (GB2.0), a comprehensive technological framework that aims to foster the exchange of standard DNA parts for plant synthetic biology. GB2.0 relies on the use of type IIS restriction enzymes for DNA assembly and proposes a modular cloning schema with positional notation that resembles the grammar of natural languages. Apart from providing an optimized cloning strategy that generates fully exchangeable genetic elements for multigene engineering, the GB2.0 toolkit offers an evergrowing open collection of DNA parts, including a group of functionally tested, premade genetic modules to build frequently used modules like constitutive and inducible expression cassettes, endogenous gene silencing and protein-protein interaction tools, etc. Use of the GB2.0 framework is facilitated by a number of Web resources that include a publicly available database, tutorials, and a software package that provides in silico simulations and laboratory protocols for GB2.0 part domestication and multigene engineering. In short, GB2.0 provides a framework to exchange both information and physical DNA elements among bioengineers to help implement plant synthetic biology projects.

Deconstructing the core dynamics from a complex time-lagged regulatory biological circuit.

PubMed

Eriksson, O; Brinne, B; Zhou, Y; Björkegren, J; Tegnér, J

2009-03-01

Complex regulatory dynamics is ubiquitous in molecular networks composed of genes and proteins. Recent progress in computational biology and its application to molecular data generate a growing number of complex networks. Yet, it has been difficult to understand the governing principles of these networks beyond graphical analysis or extensive numerical simulations. Here the authors exploit several simplifying biological circumstances which thereby enable to directly detect the underlying dynamical regularities driving periodic oscillations in a dynamical nonlinear computational model of a protein-protein network. System analysis is performed using the cell cycle, a mathematically well-described complex regulatory circuit driven by external signals. By introducing an explicit time delay and using a 'tearing-and-zooming' approach the authors reduce the system to a piecewise linear system with two variables that capture the dynamics of this complex network. A key step in the analysis is the identification of functional subsystems by identifying the relations between state-variables within the model. These functional subsystems are referred to as dynamical modules operating as sensitive switches in the original complex model. By using reduced mathematical representations of the subsystems the authors derive explicit conditions on how the cell cycle dynamics depends on system parameters, and can, for the first time, analyse and prove global conditions for system stability. The approach which includes utilising biological simplifying conditions, identification of dynamical modules and mathematical reduction of the model complexity may be applicable to other well-characterised biological regulatory circuits. [Includes supplementary material].

Microgravity

NASA Image and Video Library

2001-06-05

This computer-generated image depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Key elements are labeled in other images (0101754, 0101830, and TBD).

Microgravity

NASA Image and Video Library

2001-06-05

This computer-generated image depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Key elements are labeled in other images (0101754, 0101829, 0101830).

Microgravity

NASA Image and Video Library

2001-06-05

This computer-generated image depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. A larger image is available without labels (No. 0101755).

Implications of Green Tea and Its Constituents in the Prevention of Cancer via the Modulation of Cell Signalling Pathway

PubMed Central

Rahmani, Arshad H.; Al shabrmi, Fahad M.; Allemailem, Khaled S.; Aly, Salah M.; Khan, Masood A.

2015-01-01

Green tea is commonly used as a beverage worldwide, especially in China, Japan, Morocco, and Saudi Arabia. Green tea and its constituents have been considered very effective in the prevention and treatment of various diseases. It contains a variety of catechins, which show a pivotal role in the modulation of biological activities and also act as chemopreventive agents. Earlier studies have confirmed that green tea and its chief constituent epigallocatechin gallate (EGCG) have a potential role in the management of cancer through the modulation of cell signaling pathways. In this review, we focused on the beneficial effects of green tea and its constituents in the cancer prevention and treatment and its impact on modulation of molecular pathways. PMID:25977926

Microgravity

NASA Image and Video Library

2001-06-05

This scale model depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Key elements are labeled in other images (0101754, 0101829, 0101830, and TBD).

Molecular mechanics and dynamics characterization of an in silico mutated protein: a stand-alone lab module or support activity for in vivo and in vitro analyses of targeted proteins.

PubMed

Chiang, Harry; Robinson, Lucy C; Brame, Cynthia J; Messina, Troy C

2013-01-01

Over the past 20 years, the biological sciences have increasingly incorporated chemistry, physics, computer science, and mathematics to aid in the development and use of mathematical models. Such combined approaches have been used to address problems from protein structure-function relationships to the workings of complex biological systems. Computer simulations of molecular events can now be accomplished quickly and with standard computer technology. Also, simulation software is freely available for most computing platforms, and online support for the novice user is ample. We have therefore created a molecular dynamics laboratory module to enhance undergraduate student understanding of molecular events underlying organismal phenotype. This module builds on a previously described project in which students use site-directed mutagenesis to investigate functions of conserved sequence features in members of a eukaryotic protein kinase family. In this report, we detail the laboratory activities of a MD module that provide a complement to phenotypic outcomes by providing a hypothesis-driven and quantifiable measure of predicted structural changes caused by targeted mutations. We also present examples of analyses students may perform. These laboratory activities can be integrated with genetics or biochemistry experiments as described, but could also be used independently in any course that would benefit from a quantitative approach to protein structure-function relationships. Copyright © 2013 Wiley Periodicals, Inc.

Glycan Engineering for Cell and Developmental Biology.

PubMed

Griffin, Matthew E; Hsieh-Wilson, Linda C

2016-01-21

Cell-surface glycans are a diverse class of macromolecules that participate in many key biological processes, including cell-cell communication, development, and disease progression. Thus, the ability to modulate the structures of glycans on cell surfaces provides a powerful means not only to understand fundamental processes but also to direct activity and elicit desired cellular responses. Here, we describe methods to sculpt glycans on cell surfaces and highlight recent successes in which artificially engineered glycans have been employed to control biological outcomes such as the immune response and stem cell fate. Copyright © 2016 Elsevier Ltd. All rights reserved.

Auditory neural networks involved in attention modulation prefer biologically significant sounds and exhibit sexual dimorphism in anurans.

PubMed

Xue, Fei; Yue, Xizi; Fan, Yanzhu; Cui, Jianguo; Brauth, Steven E; Tang, Yezhong; Fang, Guangzhan

2018-03-09

Allocating attention to biologically relevant stimuli in a complex environment is critically important for survival and reproductive success. In humans, attention modulation is regulated by the frontal cortex, and is often reflected by changes in specific components of the event-related potential (ERP). Although brain networks for attention modulation have been widely studied in primates and avian species, little is known about attention modulation in amphibians. The present study aimed to investigate the attention modulation networks in an anuran species, the Emei music frog ( Babina daunchina ). Male music frogs produce advertisement calls from within underground nest burrows that modify the acoustic features of the calls, and both males and females prefer calls produced from inside burrows. We broadcast call stimuli to male and female music frogs while simultaneously recording electroencephalographic (EEG) signals from the telencephalon and mesencephalon. Granger causal connectivity analysis was used to elucidate functional brain networks within the time window of ERP components. The results show that calls produced from inside nests which are highly sexually attractive result in the strongest brain connections; both ascending and descending connections involving the left telencephalon were stronger in males while those in females were stronger with the right telencephalon. Our findings indicate that the frog brain allocates neural attention resources to highly attractive sounds within the window of early components of ERP, and that such processing is sexually dimorphic, presumably reflecting the different reproductive strategies of males and females. © 2018. Published by The Company of Biologists Ltd.

Function, dynamics and evolution of network motif modules in integrated gene regulatory networks of worm and plant.

PubMed

Defoort, Jonas; Van de Peer, Yves; Vermeirssen, Vanessa

2018-06-05

Gene regulatory networks (GRNs) consist of different molecular interactions that closely work together to establish proper gene expression in time and space. Especially in higher eukaryotes, many questions remain on how these interactions collectively coordinate gene regulation. We study high quality GRNs consisting of undirected protein-protein, genetic and homologous interactions, and directed protein-DNA, regulatory and miRNA-mRNA interactions in the worm Caenorhabditis elegans and the plant Arabidopsis thaliana. Our data-integration framework integrates interactions in composite network motifs, clusters these in biologically relevant, higher-order topological network motif modules, overlays these with gene expression profiles and discovers novel connections between modules and regulators. Similar modules exist in the integrated GRNs of worm and plant. We show how experimental or computational methodologies underlying a certain data type impact network topology. Through phylogenetic decomposition, we found that proteins of worm and plant tend to functionally interact with proteins of a similar age, while at the regulatory level TFs favor same age, but also older target genes. Despite some influence of the duplication mode difference, we also observe at the motif and module level for both species a preference for age homogeneity for undirected and age heterogeneity for directed interactions. This leads to a model where novel genes are added together to the GRNs in a specific biological functional context, regulated by one or more TFs that also target older genes in the GRNs. Overall, we detected topological, functional and evolutionary properties of GRNs that are potentially universal in all species.

Biphasic patterns of diversification and the emergence of modules

PubMed Central

Mittenthal, Jay; Caetano-Anollés, Derek; Caetano-Anollés, Gustavo

2012-01-01

The intricate molecular and cellular structure of organisms converts energy to work, which builds and maintains structure. Evolving structure implements modules, in which parts are tightly linked. Each module performs characteristic functions. In this work we propose that a module can emerge through two phases of diversification of parts. Early in the first phase of this biphasic pattern, the parts have weak linkage—they interact weakly and associate variously. The parts diversify and compete. Under selection for performance, interactions among the parts increasingly constrain their structure and associations. As many variants are eliminated, parts self-organize into modules with tight linkage. Linkage may increase in response to exogenous stresses as well as endogenous processes. In the second phase of diversification, variants of the module and its functions evolve and become new parts for a new cycle of generation of higher-level modules. This linkage hypothesis can interpret biphasic patterns in the diversification of protein domain structure, RNA and protein shapes, and networks in metabolism, codes, and embryos, and can explain hierarchical levels of structural organization that are widespread in biology. PMID:22891076

Toward modular biological models: defining analog modules based on referent physiological mechanisms

PubMed Central

2014-01-01

Background Currently, most biomedical models exist in isolation. It is often difficult to reuse or integrate models or their components, in part because they are not modular. Modular components allow the modeler to think more deeply about the role of the model and to more completely address a modeling project’s requirements. In particular, modularity facilitates component reuse and model integration for models with different use cases, including the ability to exchange modules during or between simulations. The heterogeneous nature of biology and vast range of wet-lab experimental platforms call for modular models designed to satisfy a variety of use cases. We argue that software analogs of biological mechanisms are reasonable candidates for modularization. Biomimetic software mechanisms comprised of physiomimetic mechanism modules offer benefits that are unique or especially important to multi-scale, biomedical modeling and simulation. Results We present a general, scientific method of modularizing mechanisms into reusable software components that we call physiomimetic mechanism modules (PMMs). PMMs utilize parametric containers that partition and expose state information into physiologically meaningful groupings. To demonstrate, we modularize four pharmacodynamic response mechanisms adapted from an in silico liver (ISL). We verified the modularization process by showing that drug clearance results from in silico experiments are identical before and after modularization. The modularized ISL achieves validation targets drawn from propranolol outflow profile data. In addition, an in silico hepatocyte culture (ISHC) is created. The ISHC uses the same PMMs and required no refactoring. The ISHC achieves validation targets drawn from propranolol intrinsic clearance data exhibiting considerable between-lab variability. The data used as validation targets for PMMs originate from both in vitro to in vivo experiments exhibiting large fold differences in time scale. Conclusions This report demonstrates the feasibility of PMMs and their usefulness across multiple model use cases. The pharmacodynamic response module developed here is robust to changes in model context and flexible in its ability to achieve validation targets in the face of considerable experimental uncertainty. Adopting the modularization methods presented here is expected to facilitate model reuse and integration, thereby accelerating the pace of biomedical research. PMID:25123169

Toward modular biological models: defining analog modules based on referent physiological mechanisms.

PubMed

Petersen, Brenden K; Ropella, Glen E P; Hunt, C Anthony

2014-08-16

Currently, most biomedical models exist in isolation. It is often difficult to reuse or integrate models or their components, in part because they are not modular. Modular components allow the modeler to think more deeply about the role of the model and to more completely address a modeling project's requirements. In particular, modularity facilitates component reuse and model integration for models with different use cases, including the ability to exchange modules during or between simulations. The heterogeneous nature of biology and vast range of wet-lab experimental platforms call for modular models designed to satisfy a variety of use cases. We argue that software analogs of biological mechanisms are reasonable candidates for modularization. Biomimetic software mechanisms comprised of physiomimetic mechanism modules offer benefits that are unique or especially important to multi-scale, biomedical modeling and simulation. We present a general, scientific method of modularizing mechanisms into reusable software components that we call physiomimetic mechanism modules (PMMs). PMMs utilize parametric containers that partition and expose state information into physiologically meaningful groupings. To demonstrate, we modularize four pharmacodynamic response mechanisms adapted from an in silico liver (ISL). We verified the modularization process by showing that drug clearance results from in silico experiments are identical before and after modularization. The modularized ISL achieves validation targets drawn from propranolol outflow profile data. In addition, an in silico hepatocyte culture (ISHC) is created. The ISHC uses the same PMMs and required no refactoring. The ISHC achieves validation targets drawn from propranolol intrinsic clearance data exhibiting considerable between-lab variability. The data used as validation targets for PMMs originate from both in vitro to in vivo experiments exhibiting large fold differences in time scale. This report demonstrates the feasibility of PMMs and their usefulness across multiple model use cases. The pharmacodynamic response module developed here is robust to changes in model context and flexible in its ability to achieve validation targets in the face of considerable experimental uncertainty. Adopting the modularization methods presented here is expected to facilitate model reuse and integration, thereby accelerating the pace of biomedical research.

Emerging concepts in effector biology of plant-associated organisms.

PubMed

Hogenhout, Saskia A; Van der Hoorn, Renier A L; Terauchi, Ryohei; Kamoun, Sophien

2009-02-01

Plant-associated organisms secrete proteins and other molecules to modulate plant defense circuitry and enable colonization of plant tissue. Understanding the molecular function of these secreted molecules, collectively known as effectors, became widely accepted as essential for a mechanistic understanding of the processes underlying plant colonization. This review summarizes recent findings in the field of effector biology and highlights the common concepts that have emerged from the study of cellular plant pathogen effectors.

The Role of RNA in Biological Phase Separations.

PubMed

Fay, Marta M; Anderson, Paul J

2018-05-10

Phase transitions that alter the physical state of ribonucleoprotein particles contribute to the spacial and temporal organization of the densely packed intracellular environment. This allows cells to organize biologically coupled processes as well as respond to environmental stimuli. RNA plays a key role in phase separation events that modulate various aspects of RNA metabolism. Here, we review the role that RNA plays in ribonucleoprotein phase separations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Entropy-based divergent and convergent modular pattern reveals additive and synergistic anticerebral ischemia mechanisms.

PubMed

Yu, Yanan; Zhang, Xiaoxu; Li, Bing; Zhang, Yingying; Liu, Jun; Li, Haixia; Chen, Yinying; Wang, Pengqian; Kang, Ruixia; Wu, Hongli; Wang, Zhong

2016-12-01

Module-based network analysis of diverse pharmacological mechanisms is critical to systematically understand combination therapies and disease outcomes. We first constructed drug-target ischemic networks in baicalin, jasminoidin, ursodeoxycholic acid, and their combinations baicalin and jasminoidin as well as jasminoidin and ursodeoxycholic acid groups and identified modules using the entropy-based clustering algorithm. The modules 11, 7, 4, 8 and 3 were identified as baicalin, jasminoidin, ursodeoxycholic acid, baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid-emerged responsive modules, while 12, 8, 15, 17 and 9 were identified as disappeared responsive modules based on variation of topological similarity, respectively. No overlapping differential biological processes were enriched between baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid pure emerged responsive modules, but two were enriched by their co-disappeared responsive modules including nucleotide-excision repair and epithelial structure maintenance. We found an additive effect of baicalin and jasminoidin in a divergent pattern and a synergistic effect of jasminoidin and ursodeoxycholic acid in a convergent pattern on "central hit strategy" of regulating inflammation against cerebral ischemia. The proposed module-based approach may provide us a holistic view to understand multiple pharmacological mechanisms associated with differential phenotypes from the standpoint of modular pharmacology.

Image processing and recognition for biological images.

PubMed

Uchida, Seiichi

2013-05-01

This paper reviews image processing and pattern recognition techniques, which will be useful to analyze bioimages. Although this paper does not provide their technical details, it will be possible to grasp their main tasks and typical tools to handle the tasks. Image processing is a large research area to improve the visibility of an input image and acquire some valuable information from it. As the main tasks of image processing, this paper introduces gray-level transformation, binarization, image filtering, image segmentation, visual object tracking, optical flow and image registration. Image pattern recognition is the technique to classify an input image into one of the predefined classes and also has a large research area. This paper overviews its two main modules, that is, feature extraction module and classification module. Throughout the paper, it will be emphasized that bioimage is a very difficult target for even state-of-the-art image processing and pattern recognition techniques due to noises, deformations, etc. This paper is expected to be one tutorial guide to bridge biology and image processing researchers for their further collaboration to tackle such a difficult target. © 2013 The Author Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

Fullerene mediates proliferation and cardiomyogenic differentiation of adipose-derived stem cells via modulation of MAPK pathway and cardiac protein expression

PubMed Central

Hao, Tong; Zhou, Jin; Lü, Shuanghong; Yang, Boguang; Wang, Yan; Fang, Wancai; Jiang, Xiaoxia; Lin, Qiuxia; Li, Junjie; Wang, Changyong

2016-01-01

Zero-dimensional fullerenes can modulate the biological behavior of a variety of cell lines. However, the effects and molecular mechanisms of proliferation and cardiomyogenic differentiation in brown adipose-derived stem cells (BADSCs) are still unclear. In this study, we report the initial biological effects of fullerene-C60 on BADSCs at different concentrations. Results suggest that fullerene-C60 has no cytotoxic effects on BADSCs even at a concentration of 100 μg/mL. Fullerene-C60 improves the MAPK expression level and stem cell survival, proliferation, and cardiomyogenesis. Further, we found that the fullerene-C60 modulates cardiomyogenic differentiation. Fullerene-C60 improves the expression of cardiomyocyte-specific proteins (cTnT and α-sarcomeric actinin). At elevated concentration, fullerene-C60 reduces the incidence of diminished spontaneous cardiac differentiation of BADSCs with time. At the genetic level, fullerene-C60 (5 μg/mL) also improves the expression of cTnT. In addition, fullerene-C60 promotes the formation of gap junction among cells. These findings have important implications for clinical application of fullerenes in the treatment of myocardial infarction. PMID:26848263

A preliminary investigation of the environmental Control and Life Support Subsystems (EC/LSS) for animal and plant experiment payloads

NASA Technical Reports Server (NTRS)

Wells, H. B.

1972-01-01

A preliminary study of the environmental control and life support subsystems (EC/LSS) necessary for an earth orbital spacecraft to conduct biological experiments is presented. The primary spacecraft models available for conducting these biological experiments are the space shuttle and modular space station. The experiments would be housed in a separate module that would be contained in either the shuttle payload bay or attached to the modular space station. This module would be manned only for experiment-related tasks, and would contain a separate EC/LSS for the crew and animals. Metabolic data were tabulated on various animals that are considered useful for a typical experiment program. The minimum payload for the 30-day space shuttle module was found to require about the equivalent of a one-man EC/LSS; however, the selected two-man shuttle assemblies will give a growth and contingency factor of about 50 percent. The maximum payloads for the space station mission will require at least a seven-man EC/LSS for the laboratory colony and a nine-man EC/LSS for the centrifuge colony. There is practically no room for growth or contingencies in these areas.

BioSIGHT: Interactive Visualization Modules for Science Education

NASA Technical Reports Server (NTRS)

Wong, Wee Ling

1998-01-01

Redefining science education to harness emerging integrated media technologies with innovative pedagogical goals represents a unique challenge. The Integrated Media Systems Center (IMSC) is the only engineering research center in the area of multimedia and creative technologies sponsored by the National Science Foundation. The research program at IMSC is focused on developing advanced technologies that address human-computer interfaces, database management, and high- speed network capabilities. The BioSIGHT project at IMSC is a demonstration technology project in the area of education that seeks to address how such emerging multimedia technologies can make an impact on science education. The scope of this project will help solidify NASA's commitment for the development of innovative educational resources that promotes science literacy for our students and the general population as well. These issues must be addressed as NASA marches towards the goal of enabling human space exploration that requires an understanding of life sciences in space. The IMSC BioSIGHT lab was established with the purpose of developing a novel methodology that will map a high school biology curriculum into a series of interactive visualization modules that can be easily incorporated into a space biology curriculum. Fundamental concepts in general biology must be mastered in order to allow a better understanding and application for space biology. Interactive visualization is a powerful component that can capture the students' imagination, facilitate their assimilation of complex ideas, and help them develop integrated views of biology. These modules will augment the role of the teacher and will establish the value of student-centered interactivity, both in an individual setting as well as in a collaborative learning environment. Students will be able to interact with the content material, explore new challenges, and perform virtual laboratory simulations. The BioSIGHT effort is truly cross-disciplinary in nature and requires expertise from many areas including Biology, Computer Science, Electrical Engineering, Education, and the Cognitive Sciences. The BioSIGHT team includes a scientific illustrator, educational software designer, computer programmers as well as IMSC graduate and undergraduate students. Our collaborators include TERC, a research and education organization with extensive k-12 math and science curricula development from Cambridge, MA.; SRI International of Menlo Park, CA.; teachers and students from local area high schools (Newbury Park High School, USC's Family of Five schools, Chadwick School, and Pasadena Polytechnic High School).

Tomography: Three Dimensional Image Construction. Applications of Analysis to Medical Radiology. [and] Genetic Counseling. Applications of Probability to Medicine. [and] The Design of Honeycombs. Applications of Differential Equations to Biology. Modules and Monographs in Undergraduate Mathematics and Its Applications Project. UMAP Units 318, 456, 502.

ERIC Educational Resources Information Center

Solomon, Frederick; And Others.

This document consists of three modules. The first looks at applications of analysis to medical radiology. The goals are to provide: 1) acquaintance with a significant applied mathematics problem utilizing Fourier Transforms; 2) generalization of the Fourier Transforms to two dimensions; 3) practice with Fourier Transforms; and 4) introduction to…

Identification of Novel Human Breast Carcinoma (MDA-MB-231) Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library.

PubMed

Lenci, Elena; Innocenti, Riccardo; Biagioni, Alessio; Menchi, Gloria; Bianchini, Francesca; Trabocchi, Andrea

2016-10-20

The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2 H -furo[3,2- b ][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism.

The Light Microscopy Module: An On-Orbit Multi-User Microscope Facility

NASA Technical Reports Server (NTRS)

Motil, Susan M.; Snead, John H.

2002-01-01

The Light Microscopy Module (LMM) is planned as a remotely controllable on-orbit microscope subrack facility, allowing flexible scheduling and operation of fluids and biology experiments within the Fluids and Combustion Facility (FCF) Fluids Integrated Rack (FIR) on the International Space Station (ISS). The LMM will be the first integrated payload with the FIR to conduct four fluid physics experiments. A description of the LMM diagnostic capabilities, including video microscopy, interferometry, laser tweezers, confocal, and spectrophotometry, will be provided.

Illuminating the Chemistry of Life: Design, Synthesis, and Applications of “Caged” and Related Photoresponsive Compounds

PubMed Central

Lee, Hsienming; Larson, Daniel R.; Lawrence, David S.

2009-01-01

Biological systems are characterized by a level of spatial and temporal organization that often lies beyond the grasp of present day methods. Light-modulated bioreagents, including analogs of low molecular weight compounds, peptides, proteins, and nucleic acids, represent a compelling strategy to probe, perturb, or sample biological phenomena with the requisite control to address many of these organizational complexities. Although this technology has created considerable excitement in the chemical community, its application to biological questions has been relatively limited. We describe the challenges associated with the design, synthesis, and use of light-responsive bioreagents, the scope and limitations associated with the instrumentation required for their application, and recent chemical and biological advances in this field. PMID:19298086

Illuminating the chemistry of life: design, synthesis, and applications of "caged" and related photoresponsive compounds.

PubMed

Lee, Hsien-Ming; Larson, Daniel R; Lawrence, David S

2009-06-19

Biological systems are characterized by a level of spatial and temporal organization that often lies beyond the grasp of present day methods. Light-modulated bioreagents, including analogs of low molecular weight compounds, peptides, proteins, and nucleic acids, represent a compelling strategy to probe, perturb, or sample biological phenomena with the requisite control to address many of these organizational complexities. Although this technology has created considerable excitement in the chemical community, its application to biological questions has been relatively limited. We describe the challenges associated with the design, synthesis, and use of light-responsive bioreagents; the scope and limitations associated with the instrumentation required for their application; and recent chemical and biological advances in this field.

Software Reviews.

ERIC Educational Resources Information Center

Science and Children, 1988

1988-01-01

Reviews five software packages for use with school age children. Includes "Science Toolkit Module 2: Earthquake Lab"; "Adaptations and Identification"; "Geoworld"; "Body Systems II Series: The Blood System: A Liquid of Life," all for Apple II, and "Science Courseware: Life Science/Biology" for…

A Modular Approach to Year 11 Science Courses

ERIC Educational Resources Information Center

Woolley, Terry G.

1976-01-01

Described is a secondary school science program which includes modularized courses in the earth science unified science, biology, chemistry, and physics. Students may continue in one science course or switch between courses upon completing modules. (SL)

Nanoparticles that Communicate In Vivo to Amplify Tumour Targeting

PubMed Central

von Maltzahn, Geoffrey; Park, Ji-Ho; Lin, Kevin Y.; Singh, Neetu; Schwöppe, Christian; Mesters, Rolf; Berdel, Wolfgang E.; Ruoslahti, Erkki; Sailor, Michael J.; Bhatia, Sangeeta N.

2012-01-01

Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability for communication to improve targeting in biological systems, such inflammatory cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘Signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally active the coagulation cascade to broadcast tumour location to clot-targeted ‘Receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed from multiple types of Signalling and Receiving modules, can transmit information via multiple molecular pathways in coagulation, can operate autonomously, and can target over 40-fold higher doses of chemotherapeutics to tumours than non-communicating controls. PMID:21685903

Design, Synthesis, and Biological Functionality of a Dendrimer-based Modular Drug Delivery Platform

PubMed Central

Mullen, Douglas G.; McNerny, Daniel Q.; Desai, Ankur; Cheng, Xue-min; DiMaggio, Stassi C.; Kotlyar, Alina; Zhong, Yueyang; Qin, Suyang; Kelly, Christopher V.; Thomas, Thommey P.; Majoros, Istvan; Orr, Bradford G.; Baker, James R.; Banaszak Holl, Mark M.

2011-01-01

A modular dendrimer-based drug delivery platform was designed to improve upon existing limitations in single dendrimer systems. Using this modular strategy, a biologically active platform containing receptor mediated targeting and fluorescence imaging modules was synthesized by coupling a folic acid (FA) conjugated dendrimer with a fluorescein isothiocyanate (FITC) conjugated dendrimer. The two different dendrimer modules were coupled via the 1,3-dipolar cycloaddition reaction (‘click’ chemistry) between an alkyne moiety on the surface of the first dendrimer and an azide moiety on the second dendrimer. Two simplified model systems were also synthesized to develop appropriate ‘click’ reaction conditions and aid in spectroscopic assignments. Conjugates were characterized by 1H NMR spectroscopy and NOESY. The FA-FITC modular platform was evaluated in vitro with a human epithelial cancer cell line (KB) and found to specifically target the over-expressed folic acid receptor. PMID:21425790

Adenosine A2B receptor: from cell biology to human diseases

NASA Astrophysics Data System (ADS)

Sun, Ying; Huang, Pingbo

2016-08-01

Extracellular adenosine is a ubiquitous signaling molecule that modulates a wide array of biological processes. Recently, significant advances have been made in our understanding of A2B adenosine receptor (A2BAR). In this review, we first summarize some of the general characteristics of A2BAR, and then we describe the multiple binding partners of the receptor, such as newly identified α-actinin-1 and p105, and discuss how these associated proteins could modulate A2BAR’s functions, including certain seemingly paradoxical functions of the receptor. Growing evidence indicates a critical role of A2BAR in cancer, renal disease, and diabetes, in addition to its importance in the regulation of vascular diseases and lung disease. Here, we also discuss the role of A2BAR in cancer, renal disease, and diabetes and the potential of the receptor as a target for treating these three diseases.

Natural products as an inspiration in the diversity-oriented synthesis of bioactive compound libraries

PubMed Central

Cordier, Christopher; Morton, Daniel; Murrison, Sarah; O'Leary-Steele, Catherine

2008-01-01

The purpose of diversity-oriented synthesis is to drive the discovery of small molecules with previously unknown biological functions. Natural products necessarily populate biologically relevant chemical space, since they bind both their biosynthetic enzymes and their target macromolecules. Natural product families are, therefore, libraries of pre-validated, functionally diverse structures in which individual compounds selectively modulate unrelated macromolecular targets. This review describes examples of diversity-oriented syntheses which have, to some extent, been inspired by the structures of natural products. Particular emphasis is placed on innovations that allow the synthesis of compound libraries that, like natural products, are skeletally diverse. Mimicking the broad structural features of natural products may allow the discovery of compounds that modulate the functions of macromolecules for which ligands are not known. The ability of innovations in diversity-oriented synthesis to deliver such compounds is critically assessed. PMID:18663392

Nanoparticles that communicate in vivo to amplify tumour targeting

NASA Astrophysics Data System (ADS)

von Maltzahn, Geoffrey; Park, Ji-Ho; Lin, Kevin Y.; Singh, Neetu; Schwöppe, Christian; Mesters, Rolf; Berdel, Wolfgang E.; Ruoslahti, Erkki; Sailor, Michael J.; Bhatia, Sangeeta N.

2011-07-01

Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability of communication to improve targeting in biological systems, such as inflammatory-cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally activate the coagulation cascade to broadcast tumour location to clot-targeted ‘receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed of multiple types of signalling and receiving modules, can transmit information through multiple molecular pathways in coagulation, can operate autonomously and can target over 40 times higher doses of chemotherapeutics to tumours than non-communicating controls.

Low concentrations of copper in drinking water increase AP-1 binding in the brain.

PubMed

Lung, Shyang; Li, Huihui; Bondy, Stephen C; Campbell, Arezoo

2015-12-01

Copper (Cu) in trace amounts is essential for biological organisms. However, dysregulation of the redox-active metal has been implicated in different neurological disorders such as Wilson's, Menkes', Alzheimer's, and Parkinson's diseases. Since many households use Cu tubing in the plumbing system, and corrosion causes the metal to leach into the drinking water, there may be adverse effects on the central nervous system connected with low-level chronic exposure. The present study demonstrates that treatment with a biologically relevant concentration of Cu for 3 months significantly increases activation of the redox-modulated transcription factor AP-1 in mouse brains. This was independent of an upstream kinase indicated in AP-1 activation. Another redox-active transcription factor, NF-κB, was not significantly modified by the Cu exposure. These results indicate that the effect of Cu on AP-1 is unique and may involve direct modulation of DNA binding. © The Author(s) 2012.

Cot/tpl2 participates in the activation of macrophages by adiponectin.

PubMed

Sanz-Garcia, Carlos; Nagy, Laura E; Lasunción, Miguel A; Fernandez, Margarita; Alemany, Susana

2014-06-01

Whereas the main function of APN is to enhance insulin activity, it is also involved in modulating the macrophage phenotype. Here, we demonstrate that at physiological concentrations, APN activates Erk1/2 via the IKKβ-p105/NF-κΒ1-Cot/tpl2 intracellular signal transduction cassette in macrophages. In peritoneal macrophages stimulated with APN, Cot/tpl2 influences the ability to phagocytose beads. However, Cot/tpl2 did not modulate the known capacity of APN to decrease lipid content in peritoneal macrophages in response to treatment with oxLDL or acLDL. A microarray analysis of gene-expression profiles in BMDMs exposed to APN revealed that APN modulated the expression of ∼3300 genes; the most significantly affected biological functions were the inflammatory and the infectious disease responses. qRT-PCR analysis of WT and Cot/tpl2 KO macrophages stimulated with APN for 0, 3, and 18 h revealed that Cot/tpl2 participated in the up-regulation of APN target inflammatory mediators included in the cytokine-cytokine receptor interaction pathway (KEGG ID 4060). In accordance with these data, macrophages stimulated with APN increased secretion of cytokines and chemokines, including IL-1β, IL-1α, TNF-α, IL-10, IL-12, IL-6, and CCL2. Moreover, Cot/tpl2 also played an important role in the production of these inflammatory mediators upon stimulation of macrophages with APN. It has been reported that different types of signals that stimulate TLRs, IL-1R, TNFR, FcγR, and proteinase-activated receptor-1 activate Cot/tpl2. Here, we demonstrate that APN is a new signal that activates the IKKβ-p105/NF-κΒ1-Cot/tpl2-MKK1/2-Erk1/2 axis in macrophages. Furthermore, this signaling cassette modulates the biological functions triggered by APN in macrophages. © 2014 Society for Leukocyte Biology.

Higher Order Chromatin Modulator Cohesin SA1 Is an Early Biomarker for Colon Carcinogenesis: Race-Specific Implications.

PubMed

Wali, Ramesh K; Momi, Navneet; Dela Cruz, Mart; Calderwood, Audrey H; Stypula-Cyrus, Yolanda; Almassalha, Luay; Chhaparia, Anuj; Weber, Christopher R; Radosevich, Andrew; Tiwari, Ashish K; Latif, Bilal; Backman, Vadim; Roy, Hemant K

2016-11-01

Alterations in high order chromatin, with concomitant modulation in gene expression, are one of the earliest events in the development of colorectal cancer. Cohesins are a family of proteins that modulate high-order chromatin, although the role in colorectal cancer remains incompletely understood. We, therefore, assessed the role of cohesin SA1 in colorectal cancer biology and as a biomarker focusing in particular on the increased incidence/mortality of colorectal cancer among African-Americans. Immunohistochemistry on tissue arrays revealed dramatically decreased SA1 expression in both adenomas (62%; P = 0.001) and adenocarcinomas (75%; P = 0.0001). RT-PCR performed in endoscopically normal rectal biopsies (n = 78) revealed a profound decrease in SA1 expression in adenoma-harboring patients (field carcinogenesis) compared with those who were neoplasia-free (47%; P = 0.03). From a racial perspective, colorectal cancer tissues from Caucasians had 56% higher SA1 expression than in African-Americans. This was mirrored in field carcinogenesis where healthy Caucasians expressed more SA1 at baseline compared with matched African-American subjects (73%; P = 0.003). However, as a biomarker for colorectal cancer risk, the diagnostic performance as assessed by area under ROC curve was greater in African-Americans (AUROC = 0.724) than in Caucasians (AUROC = 0.585). From a biologic perspective, SA1 modulation of high-order chromatin was demonstrated with both biophotonic (nanocytology) and chromatin accessibility [micrococcal nuclease (MNase)] assays in SA1-knockdown HT29 colorectal cancer cells. The functional consequences were underscored by increased proliferation (WST-1; P = 0.0002, colony formation; P = 0.001) in the SA1-knockdown HT29 cells. These results provide the first evidence indicating a tumor suppressor role of SA1 in early colon carcinogenesis and as a risk stratification biomarker giving potential insights into biologic basis of racial disparities in colorectal cancer. Cancer Prev Res; 9(11); 844-54. ©2016 AACR. ©2016 American Association for Cancer Research.

Interacting Network of the Gap Junction (GJ) Protein Connexin43 (Cx43) is Modulated by Ischemia and Reperfusion in the Heart.

PubMed

Martins-Marques, Tania; Anjo, Sandra Isabel; Pereira, Paulo; Manadas, Bruno; Girão, Henrique

2015-11-01

The coordinated and synchronized cardiac muscle contraction relies on an efficient gap junction-mediated intercellular communication (GJIC) between cardiomyocytes, which involves the rapid anisotropic impulse propagation through connexin (Cx)-containing channels, namely of Cx43, the most abundant Cx in the heart. Expectedly, disturbing mechanisms that affect channel activity, localization and turnover of Cx43 have been implicated in several cardiomyopathies, such as myocardial ischemia. Besides gap junction-mediated intercellular communication, Cx43 has been associated with channel-independent functions, including modulation of cell adhesion, differentiation, proliferation and gene transcription. It has been suggested that the role played by Cx43 is dictated by the nature of the proteins that interact with Cx43. Therefore, the characterization of the Cx43-interacting network and its dynamics is vital to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication, but also to unveil novel and unanticipated biological functions of Cx43. In the present report, we applied a quantitative SWATH-MS approach to characterize the Cx43 interactome in rat hearts subjected to ischemia and ischemia-reperfusion. Our results demonstrate that, in the heart, Cx43 interacts with proteins related with various biological processes such as metabolism, signaling and trafficking. The interaction of Cx43 with proteins involved in gene transcription strengthens the emerging concept that Cx43 has a role in gene expression regulation. Importantly, our data shows that the interactome of Cx43 (Connexome) is differentially modulated in diseased hearts. Overall, the characterization of Cx43-interacting network may contribute to the establishment of new therapeutic targets to modulate cardiac function in physiological and pathological conditions. Data are available via ProteomeXchange with identifier PXD002331. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Integrative systems and synthetic biology of cell-matrix adhesion sites.

PubMed

Zamir, Eli

2016-09-02

The complexity of cell-matrix adhesion convolves its roles in the development and functioning of multicellular organisms and their evolutionary tinkering. Cell-matrix adhesion is mediated by sites along the plasma membrane that anchor the actin cytoskeleton to the matrix via a large number of proteins, collectively called the integrin adhesome. Fundamental challenges for understanding how cell-matrix adhesion sites assemble and function arise from their multi-functionality, rapid dynamics, large number of components and molecular diversity. Systems biology faces these challenges in its strive to understand how the integrin adhesome gives rise to functional adhesion sites. Synthetic biology enables engineering intracellular modules and circuits with properties of interest. In this review I discuss some of the fundamental questions in systems biology of cell-matrix adhesion and how synthetic biology can help addressing them.

Genomes, Proteomes and the Central Dogma

PubMed Central

Franklin, Sarah; Vondriska, Thomas M.

2011-01-01

Systems biology, with its associated technologies of proteomics, genomics and metabolomics, is driving the evolution of our understanding of cardiovascular physiology. Rather than studying individual molecules or even single reactions, a systems approach allows integration of orthogonal datasets from distinct tiers of biological data, including gene, RNA, protein, metabolite and other component networks. Together these networks give rise to emergent properties of cellular function and it is their reprogramming that causes disease. We present five observations regarding how systems biology is guiding a revisiting of the central dogma: (i) de-emphasizing the unidirectional flow of information from genes to proteins; (ii) revealing the role of modules of molecules as opposed to individual proteins acting in isolation; (iii) enabling discovery of novel emergent properties; (iv) demonstrating the importance of networks in biology; and (v) adding new dimensionality to the study of biological systems. PMID:22010165

Microengineering as a tool to study substratum modulation and cell behaviour.

PubMed

Keatch, R P; Armoogum, K; Schor, S L; Pridham, M S; Banks, K; Khor, T Y; Matthew, C

2002-01-01

This research is an investigation of the means by which geometrical parameters (e.g. area and shape) and various surface attributes (materials and surface finish) of microengineered structures can modulate cellular response. This is based on biological observations indicating that: (i) the response of tissue cells to injury is determined by the net signal transduction response elicited by soluble regulatory molecules (e.g. cytokines), (ii) common matrix constituents (e.g. collagen) directly affect cell behaviour by the same signal transduction mechanisms mediating cytokine bioactivity, (iii) cellular response to cytokines is modulated by the precise nature of the extracellular matrix to which the target cells are adherent, including its biochemical composition and physical structure.

The Light Microscopy Module Design and Performance Demonstrations

NASA Technical Reports Server (NTRS)

Motil, Susan M.; Snead, John H.; Griffin, DeVon W.; Hovenac, Edward A.

2003-01-01

The Light Microscopy Module (LMM) is a state-of-the-art space station payload to provide investigations in the fields of fluids, condensed matter physics, and biological sciences. The LMM hardware will reside inside the Fluids Integrated Rack (FIR), a multi-user facility class payload that will provide fundamental services for the LMM and future payloads. LMM and FIR will be launched in 2005 and both will reside in the Destiny module of the International Space Station (ISS). There are five experiments to be performed within the LMM. This paper will provide a description of the initial five experiments: the supporting FIR subsystems; LMM design; capabilities and key features; and a summary of performance demonstrations.

MS Anderson checks on the CEBAS

NASA Image and Video Library

1998-01-22

STS089-357-003 (22-31 Jan. 1998) --- Astronaut Michael P. Anderson, STS-89 mission specialist, works on Endeavour's middeck with the Closed Equilibrated Biological Aquatic System (CEBAS), an experiment developed by the German Space Agency (DLR). The CEBAS mini-module, a middeck habitat for aquatic organisms, enables scientists to conduct various gravity-related experiments in the areas of zoology, botany and developmental biology, as well as in interdisciplinary areas such as scientific research on artificial ecosystems. Photo credit: NASA

Visual Cortex Inspired CNN Model for Feature Construction in Text Analysis

PubMed Central

Fu, Hongping; Niu, Zhendong; Zhang, Chunxia; Ma, Jing; Chen, Jie

2016-01-01

Recently, biologically inspired models are gradually proposed to solve the problem in text analysis. Convolutional neural networks (CNN) are hierarchical artificial neural networks, which include a various of multilayer perceptrons. According to biological research, CNN can be improved by bringing in the attention modulation and memory processing of primate visual cortex. In this paper, we employ the above properties of primate visual cortex to improve CNN and propose a biological-mechanism-driven-feature-construction based answer recommendation method (BMFC-ARM), which is used to recommend the best answer for the corresponding given questions in community question answering. BMFC-ARM is an improved CNN with four channels respectively representing questions, answers, asker information and answerer information, and mainly contains two stages: biological mechanism driven feature construction (BMFC) and answer ranking. BMFC imitates the attention modulation property by introducing the asker information and answerer information of given questions and the similarity between them, and imitates the memory processing property through bringing in the user reputation information for answerers. Then the feature vector for answer ranking is constructed by fusing the asker-answerer similarities, answerer's reputation and the corresponding vectors of question, answer, asker, and answerer. Finally, the Softmax is used at the stage of answer ranking to get best answers by the feature vector. The experimental results of answer recommendation on the Stackexchange dataset show that BMFC-ARM exhibits better performance. PMID:27471460

Visual Cortex Inspired CNN Model for Feature Construction in Text Analysis.

PubMed

Fu, Hongping; Niu, Zhendong; Zhang, Chunxia; Ma, Jing; Chen, Jie

2016-01-01

Recently, biologically inspired models are gradually proposed to solve the problem in text analysis. Convolutional neural networks (CNN) are hierarchical artificial neural networks, which include a various of multilayer perceptrons. According to biological research, CNN can be improved by bringing in the attention modulation and memory processing of primate visual cortex. In this paper, we employ the above properties of primate visual cortex to improve CNN and propose a biological-mechanism-driven-feature-construction based answer recommendation method (BMFC-ARM), which is used to recommend the best answer for the corresponding given questions in community question answering. BMFC-ARM is an improved CNN with four channels respectively representing questions, answers, asker information and answerer information, and mainly contains two stages: biological mechanism driven feature construction (BMFC) and answer ranking. BMFC imitates the attention modulation property by introducing the asker information and answerer information of given questions and the similarity between them, and imitates the memory processing property through bringing in the user reputation information for answerers. Then the feature vector for answer ranking is constructed by fusing the asker-answerer similarities, answerer's reputation and the corresponding vectors of question, answer, asker, and answerer. Finally, the Softmax is used at the stage of answer ranking to get best answers by the feature vector. The experimental results of answer recommendation on the Stackexchange dataset show that BMFC-ARM exhibits better performance.

Femtosecond laser microstructured Alumina toughened Zirconia: A new strategy to improve osteogenic differentiation of hMSCs

NASA Astrophysics Data System (ADS)

Carvalho, Angela; Cangueiro, Liliana; Oliveira, Vítor; Vilar, Rui; Fernandes, Maria H.; Monteiro, Fernando J.

2018-03-01

The use of topographic patterns has been a continuously growing area of research for tissue engineering and it is widely accepted that the surface topography of biomaterials can influence and modulate the initial biological response. Ultrafast lasers are extremely powerful tools to machine and pattern the surface of a wide range of biomaterials, however, only few work has been performed on ceramics with the intent of biomedical applications, and the biological characterization of these structured materials is scarce. In this work, relevance is given to the biological performance of such materials. A femtosecond laser ablation technique was used to modify Alumina toughened Zirconia (ATZ) surface topography, developing surfaces structured at the micro and nanoscale levels (μATZ), in a controlled and reproducible manner. Materials characterization was performed before and after laser treatment, and both materials were compared in terms of osteogenic response of human bone marrow derived mesenchymal stem cells cultured under basal conditions, expecting that the micro/nanofeatures will improve the biological response of cells. Cells metabolic activity and proliferation increased with the culture time and surface microtopography modulated cells alignment and guided proliferation. The modified surface, displayed significantly higher expression of osteogenic transcription factors and genes and, additionally, the formation of a mineralized extracellular matrix, when compared to the control surface, i.e. unmodified ATZ.

Analysis Tools for Interconnected Boolean Networks With Biological Applications.

PubMed

Chaves, Madalena; Tournier, Laurent

2018-01-01

Boolean networks with asynchronous updates are a class of logical models particularly well adapted to describe the dynamics of biological networks with uncertain measures. The state space of these models can be described by an asynchronous state transition graph, which represents all the possible exits from every single state, and gives a global image of all the possible trajectories of the system. In addition, the asynchronous state transition graph can be associated with an absorbing Markov chain, further providing a semi-quantitative framework where it becomes possible to compute probabilities for the different trajectories. For large networks, however, such direct analyses become computationally untractable, given the exponential dimension of the graph. Exploiting the general modularity of biological systems, we have introduced the novel concept of asymptotic graph , computed as an interconnection of several asynchronous transition graphs and recovering all asymptotic behaviors of a large interconnected system from the behavior of its smaller modules. From a modeling point of view, the interconnection of networks is very useful to address for instance the interplay between known biological modules and to test different hypotheses on the nature of their mutual regulatory links. This paper develops two new features of this general methodology: a quantitative dimension is added to the asymptotic graph, through the computation of relative probabilities for each final attractor and a companion cross-graph is introduced to complement the method on a theoretical point of view.

Recovery - Apollo 11

NASA Image and Video Library

1969-07-24

S69-21698 (24 July 1969) --- The three Apollo 11 crew men await pickup by a helicopter from the USS Hornet, prime recovery ship for the historic Apollo 11 lunar landing mission. The fourth man in the life raft is a United States Navy underwater demolition team swimmer. All four men are wearing biological isolation garments. Apollo 11, with astronauts Neil A. Armstrong, commander; Michael Collins, command module pilot; and Edwin E. Aldrin Jr., lunar module pilot, onboard, splashed down at 11:49 a.m. (CDT), July 24, 1969, about 812 nautical miles southwest of Hawaii and only 12 nautical miles from the USS Hornet. While astronauts Armstrong and Aldrin descended in the Lunar Module (LM) "Eagle" to explore the Sea of Tranquility region of the moon, astronaut Collins remained with the Command and Service Modules (CSM) "Columbia" in lunar orbit.

Texturing Silicon Nanowires for Highly Localized Optical Modulation of Cellular Dynamics.

PubMed

Fang, Yin; Jiang, Yuanwen; Acaron Ledesma, Hector; Yi, Jaeseok; Gao, Xiang; Weiss, Dara E; Shi, Fengyuan; Tian, Bozhi

2018-06-18

Engineered silicon-based materials can display photoelectric and photothermal responses under light illumination, which may lead to further innovations at the silicon-biology interfaces. Silicon nanowires have small radial dimensions, promising as highly localized cellular modulators, however the single crystalline form typically has limited photothermal efficacy due to the poor light absorption and fast heat dissipation. In this work, we report strategies to improve the photothermal response from silicon nanowires by introducing nanoscale textures on the surface and in the bulk. We next demonstrate high-resolution extracellular modulation of calcium dynamics in a number of mammalian cells including glial cells, neurons, and cancer cells. The new materials may be broadly used in probing and modulating electrical and chemical signals at the subcellular length scale, which is currently a challenge in the field of electrophysiology or cellular engineering.

Numerical modeling of two-photon focal modulation microscopy with a sinusoidal phase filter.

PubMed

Chen, Rui; Shen, Shuhao; Chen, Nanguang

2018-05-01

A spatiotemporal phase modulator (STPM) is theoretically investigated using the vectorial diffraction theory. The STPM is equivalent to a time-dependent phase-only pupil filter that alternates between a homogeneous filter and a stripe-shaped filter with a sinusoidal phase distribution. It is found that two-photon focal modulation microscopy (TPFMM) using this STPM can significantly suppress the background contribution from out-of-focus ballistic excitation and achieve almost the same resolution as two-photon microscopy. The modulation depth is also evaluated and a compromise exists between the signal-to-background ratio and signal-to-noise ratio. The theoretical investigations provide important insights into future implementations of TPFMM and its potential to further extend the penetration depth of nonlinear microscopy in imaging multiple-scattering biological tissues. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Materials Science Research Rack-1 (MSRR-1)

NASA Technical Reports Server (NTRS)

2001-01-01

This computer-generated image depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Key elements are labeled in other images (0101754, 0101829, 0101830, and TBD).

Materials Science Research Rack-1 (MSRR-1)

NASA Technical Reports Server (NTRS)

2001-01-01

This computer-generated image depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. A larger image is available without labels (No. 0101755).

Materials Science Research Rack-1 (MSRR-1)

NASA Technical Reports Server (NTRS)

2001-01-01

This computer-generated image depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Key elements are labeled in other images (0101754, 0101830, and TBD).

Materials Science Research Rack-1 (MSRR-1)

NASA Technical Reports Server (NTRS)

2001-01-01

This scale model depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Key elements are labeled in other images (0101754, 0101829, 0101830, and TBD).

Materials Science Research Rack-1 (MSRR-1)

NASA Technical Reports Server (NTRS)

2001-01-01

This computer-generated image depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Key elements are labeled in other images (0101754, 0101829, 0101830).

Microgravity

NASA Image and Video Library

2001-06-05

This scale model depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Here the transparent furnace is extracted for servicing. Key elements are labeled in other images (0101754, 0101829, 0101830, and TBD).

Image restoration approach to address reduced modulation contrast in structured illumination microscopy

PubMed Central

Patwary, Nurmohammed; Doblas, Ana; Preza, Chrysanthe

2018-01-01

The performance of structured illumination microscopy (SIM) is hampered in many biological applications due to the inability to modulate the light when imaging deep into the sample. This is in part because sample-induced aberration reduces the modulation contrast of the structured pattern. In this paper, we present an image restoration approach suitable for processing raw incoherent-grid-projection SIM data with a low fringe contrast. Restoration results from simulated and experimental ApoTome SIM data show results with improved signal-to-noise ratio (SNR) and optical sectioning compared to the results obtained from existing methods, such as 2D demodulation and 3D SIM deconvolution. Our proposed method provides satisfactory results (quantified by the achieved SNR and normalized mean square error) even when the modulation contrast of the illumination pattern is as low as 7%. PMID:29675307

Biochip scanner device

DOEpatents

Perov, Alexander; Belgovskiy, Alexander I.; Mirzabekov, Andrei D.

2001-01-01

A biochip scanner device used to detect and acquire fluorescence signal data from biological microchips or biochips and method of use are provided. The biochip scanner device includes a laser for emitting a laser beam. A modulator, such as an optical chopper modulates the laser beam. A scanning head receives the modulated laser beam and a scanning mechanics coupled to the scanning head moves the scanning head relative to the biochip. An optical fiber delivers the modulated laser beam to the scanning head. The scanning head collects the fluorescence light from the biochip, launches it into the same optical fiber, which delivers the fluorescence into a photodetector, such as a photodiode. The biochip scanner device is used in a row scanning method to scan selected rows of the biochip with the laser beam size matching the size of the immobilization site.

Genome-wide inference of regulatory networks in Streptomyces coelicolor.

PubMed

Castro-Melchor, Marlene; Charaniya, Salim; Karypis, George; Takano, Eriko; Hu, Wei-Shou

2010-10-18

The onset of antibiotics production in Streptomyces species is co-ordinated with differentiation events. An understanding of the genetic circuits that regulate these coupled biological phenomena is essential to discover and engineer the pharmacologically important natural products made by these species. The availability of genomic tools and access to a large warehouse of transcriptome data for the model organism, Streptomyces coelicolor, provides incentive to decipher the intricacies of the regulatory cascades and develop biologically meaningful hypotheses. In this study, more than 500 samples of genome-wide temporal transcriptome data, comprising wild-type and more than 25 regulatory gene mutants of Streptomyces coelicolor probed across multiple stress and medium conditions, were investigated. Information based on transcript and functional similarity was used to update a previously-predicted whole-genome operon map and further applied to predict transcriptional networks constituting modules enriched in diverse functions such as secondary metabolism, and sigma factor. The predicted network displays a scale-free architecture with a small-world property observed in many biological networks. The networks were further investigated to identify functionally-relevant modules that exhibit functional coherence and a consensus motif in the promoter elements indicative of DNA-binding elements. Despite the enormous experimental as well as computational challenges, a systems approach for integrating diverse genome-scale datasets to elucidate complex regulatory networks is beginning to emerge. We present an integrated analysis of transcriptome data and genomic features to refine a whole-genome operon map and to construct regulatory networks at the cistron level in Streptomyces coelicolor. The functionally-relevant modules identified in this study pose as potential targets for further studies and verification.

Dynamic Clamp in Cardiac and Neuronal Systems Using RTXI

PubMed Central

Ortega, Francis A.; Butera, Robert J.; Christini, David J.; White, John A.; Dorval, Alan D.

2016-01-01

The injection of computer-simulated conductances through the dynamic clamp technique has allowed researchers to probe the intercellular and intracellular dynamics of cardiac and neuronal systems with great precision. By coupling computational models to biological systems, dynamic clamp has become a proven tool in electrophysiology with many applications, such as generating hybrid networks in neurons or simulating channelopathies in cardiomyocytes. While its applications are broad, the approach is straightforward: synthesizing traditional patch clamp, computational modeling, and closed-loop feedback control to simulate a cellular conductance. Here, we present two example applications: artificial blocking of the inward rectifier potassium current in a cardiomyocyte and coupling of a biological neuron to a virtual neuron through a virtual synapse. The design and implementation of the necessary software to administer these dynamic clamp experiments can be difficult. In this chapter, we provide an overview of designing and implementing a dynamic clamp experiment using the Real-Time eXperiment Interface (RTXI), an open- source software system tailored for real-time biological experiments. We present two ways to achieve this using RTXI’s modular format, through the creation of a custom user-made module and through existing modules found in RTXI’s online library. PMID:25023319

In silico evolution of the hunchback gene indicates redundancy in cis-regulatory organization and spatial gene expression

PubMed Central

Zagrijchuk, Elizaveta A.; Sabirov, Marat A.; Holloway, David M.; Spirov, Alexander V.

2014-01-01

Biological development depends on the coordinated expression of genes in time and space. Developmental genes have extensive cis-regulatory regions which control their expression. These regions are organized in a modular manner, with different modules controlling expression at different times and locations. Both how modularity evolved and what function it serves are open questions. We present a computational model for the cis-regulation of the hunchback (hb) gene in the fruit fly (Drosophila). We simulate evolution (using an evolutionary computation approach from computer science) to find the optimal cis-regulatory arrangements for fitting experimental hb expression patterns. We find that the cis-regulatory region tends to readily evolve modularity. These cis-regulatory modules (CRMs) do not tend to control single spatial domains, but show a multi-CRM/multi-domain correspondence. We find that the CRM-domain correspondence seen in Drosophila evolves with a high probability in our model, supporting the biological relevance of the approach. The partial redundancy resulting from multi-CRM control may confer some biological robustness against corruption of regulatory sequences. The technique developed on hb could readily be applied to other multi-CRM developmental genes. PMID:24712536

Network Approach to Disease Diagnosis

NASA Astrophysics Data System (ADS)

Sharma, Amitabh; Bashan, Amir; Barabasi, Alber-Laszlo

2014-03-01

Human diseases could be viewed as perturbations of the underlying biological system. A thorough understanding of the topological and dynamical properties of the biological system is crucial to explain the mechanisms of many complex diseases. Recently network-based approaches have provided a framework for integrating multi-dimensional biological data that results in a better understanding of the pathophysiological state of complex diseases. Here we provide a network-based framework to improve the diagnosis of complex diseases. This framework is based on the integration of transcriptomics and the interactome. We analyze the overlap between the differentially expressed (DE) genes and disease genes (DGs) based on their locations in the molecular interaction network (''interactome''). Disease genes and their protein products tend to be much more highly connected than random, hence defining a disease sub-graph (called disease module) in the interactome. DE genes, even though different from the known set of DGs, may be significantly associated with the disease when considering their closeness to the disease module in the interactome. This new network approach holds the promise to improve the diagnosis of patients who cannot be diagnosed using conventional tools. Support was provided by HL066289 and HL105339 grants from the U.S. National Institutes of Health.

Investigative cases and student outcomes in an upper-division cell and molecular biology laboratory course at a minority-serving institution.

PubMed

Knight, Jonathan D; Fulop, Rebecca M; Márquez-Magaña, Leticia; Tanner, Kimberly D

2008-01-01

Active-learning strategies are increasingly being integrated into college-level science courses to make material more accessible to all students and to improve learning outcomes. One active-learning pedagogy, case-based learning (CBL), was developed as a way to both enhance engagement in the material and to accommodate diverse learning styles. Yet, adoption of CBL approaches in undergraduate biology courses has been piecemeal, in part because of the perceived investment of time required. Furthermore, few CBL lesson plans have been developed specifically for upper-division laboratory courses. Here, we describe four cases that we developed and implemented for a senior cell and molecular biology laboratory course at San Francisco State University, a minority-serving institution. To evaluate the effectiveness of these modules, we used both written and verbal assessments to gauge learning outcomes and attitudinal responses of students over two semesters. Students responded positively to the new approach and seemed to meet the learning goals for the course. Most said they would take a course using CBL again. These case modules are readily adaptable to a variety of classroom settings.

Investigative Cases and Student Outcomes in an Upper-Division Cell and Molecular Biology Laboratory Course at a Minority-serving Institution

PubMed Central

Fulop, Rebecca M.; Márquez-Magaña, Leticia; Tanner, Kimberly D.

2008-01-01

Active-learning strategies are increasingly being integrated into college-level science courses to make material more accessible to all students and to improve learning outcomes. One active-learning pedagogy, case-based learning (CBL), was developed as a way to both enhance engagement in the material and to accommodate diverse learning styles. Yet, adoption of CBL approaches in undergraduate biology courses has been piecemeal, in part because of the perceived investment of time required. Furthermore, few CBL lesson plans have been developed specifically for upper-division laboratory courses. Here, we describe four cases that we developed and implemented for a senior cell and molecular biology laboratory course at San Francisco State University, a minority-serving institution. To evaluate the effectiveness of these modules, we used both written and verbal assessments to gauge learning outcomes and attitudinal responses of students over two semesters. Students responded positively to the new approach and seemed to meet the learning goals for the course. Most said they would take a course using CBL again. These case modules are readily adaptable to a variety of classroom settings. PMID:19047425

Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement

PubMed Central

Goodman, S. B.; Gibon, E.; Pajarinen, J.; Lin, T.-H.; Keeney, M.; Ren, P.-G.; Nich, C.; Yao, Z.; Egashira, K.; Yang, F.; Konttinen, Y. T.

2014-01-01

Wear particles and by-products from joint replacements and other orthopaedic implants may result in a local chronic inflammatory and foreign body reaction. This may lead to persistent synovitis resulting in joint pain and swelling, periprosthetic osteolysis, implant loosening and pathologic fracture. Strategies to modulate the adverse effects of wear debris may improve the function and longevity of joint replacements and other orthopaedic implants, potentially delaying or avoiding complex revision surgical procedures. Three novel biological strategies to mitigate the chronic inflammatory reaction to orthopaedic wear particles are reported. These include (i) interference with systemic macrophage trafficking to the local implant site, (ii) modulation of macrophages from an M1 (pro-inflammatory) to an M2 (anti-inflammatory, pro-tissue healing) phenotype in the periprosthetic tissues, and (iii) local inhibition of the transcription factor nuclear factor kappa B (NF-κB) by delivery of an NF-κB decoy oligodeoxynucleotide, thereby interfering with the production of pro-inflammatory mediators. These three approaches have been shown to be viable strategies for mitigating the undesirable effects of wear particles in preclinical studies. Targeted local delivery of specific biologics may potentially extend the lifetime of orthopaedic implants. PMID:24478281

Handling gene and protein names in the age of bioinformatics: the special challenge of secreted multimodular bacterial enzymes such as the cbhA/cbh9A gene of Clostridium thermocellum.

PubMed

Schwarz, Wolfgang H; Brunecky, Roman; Broeker, Jannis; Liebl, Wolfgang; Zverlov, Vladimir V

2018-02-26

An increasing number of researchers working in biology, biochemistry, biotechnology, bioengineering, bioinformatics and other related fields of science are using biological molecules. As the scientific background of the members of different scientific communities is more diverse than ever before, the number of scientists not familiar with the rules for non-ambiguous designation of genetic elements is increasing. However, with biological molecules gaining importance through biotechnology, their functional and unambiguous designation is vital. Unfortunately, naming genes and proteins is not an easy task. In addition, the traditional concepts of bioinformatics are challenged with the appearance of proteins comprising different modules with a respective function in each module. This article highlights basic rules and novel solutions in designation recently used within the community of bacterial geneticists, and we discuss the present-day handling of gene and protein designations. As an example we will utilize a recent mischaracterization of gene nomenclature. We make suggestions for better handling of names in future literature as well as in databases and annotation projects. Our methodology emphasizes the hydrolytic function of multi-modular genes and extracellular proteins from bacteria.

Multiview hyperspectral topography of tissue structural and functional characteristics

NASA Astrophysics Data System (ADS)

Liu, Peng; Huang, Jiwei; Zhang, Shiwu; Xu, Ronald X.

2016-01-01

Accurate and in vivo characterization of structural, functional, and molecular characteristics of biological tissue will facilitate quantitative diagnosis, therapeutic guidance, and outcome assessment in many clinical applications, such as wound healing, cancer surgery, and organ transplantation. We introduced and tested a multiview hyperspectral imaging technique for noninvasive topographic imaging of cutaneous wound oxygenation. The technique integrated a multiview module and a hyperspectral module in a single portable unit. Four plane mirrors were cohered to form a multiview reflective mirror set with a rectangular cross section. The mirror set was placed between a hyperspectral camera and the target biological tissue. For a single image acquisition task, a hyperspectral data cube with five views was obtained. The five-view hyperspectral image consisted of a main objective image and four reflective images. Three-dimensional (3-D) topography of the scene was achieved by correlating the matching pixels between the objective image and the reflective images. 3-D mapping of tissue oxygenation was achieved using a hyperspectral oxygenation algorithm. The multiview hyperspectral imaging technique was validated in a wound model, a tissue-simulating blood phantom, and in vivo biological tissue. The experimental results demonstrated the technical feasibility of using multiview hyperspectral imaging for 3-D topography of tissue functional properties.

NF-κB transcriptional activity is modulated by FK506-binding proteins FKBP51 and FKBP52: a role for peptidyl-prolyl isomerase activity.

PubMed

Erlejman, Alejandra G; De Leo, Sonia A; Mazaira, Gisela I; Molinari, Alejandro M; Camisay, María Fernanda; Fontana, Vanina; Cox, Marc B; Piwien-Pilipuk, Graciela; Galigniana, Mario D

2014-09-19

Hsp90 binding immunophilins FKBP51 and FKBP52 modulate steroid receptor trafficking and hormone-dependent biological responses. With the purpose to expand this model to other nuclear factors that are also subject to nuclear-cytoplasmic shuttling, we analyzed whether these immunophilins modulate NF-κB signaling. It is demonstrated that FKBP51 impairs both the nuclear translocation rate of NF-κB and its transcriptional activity. The inhibitory action of FKBP51 requires neither the peptidylprolyl-isomerase activity of the immunophilin nor its association with Hsp90. The TPR domain of FKBP51 is essential. On the other hand, FKBP52 favors the nuclear retention time of RelA, its association to a DNA consensus binding sequence, and NF-κB transcriptional activity, the latter effect being strongly dependent on the peptidylprolyl-isomerase activity and also on the TPR domain of FKBP52, but its interaction with Hsp90 is not required. In unstimulated cells, FKBP51 forms endogenous complexes with cytoplasmic RelA. Upon cell stimulation with phorbol ester, the NF-κB soluble complex exchanges FKBP51 for FKBP52, and the NF-κB biological effect is triggered. Importantly, FKBP52 is functionally recruited to the promoter region of NF-κB target genes, whereas FKBP51 is released. Competition assays demonstrated that both immunophilins antagonize one another, and binding assays with purified proteins suggest that the association of RelA and immunophilins could be direct. These observations suggest that the biological action of NF-κB in different cell types could be positively regulated by a high FKBP52/FKBP51 expression ratio by favoring NF-κB nuclear retention, recruitment to the promoter regions of target genes, and transcriptional activity. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

SBEToolbox: A Matlab Toolbox for Biological Network Analysis

PubMed Central

Konganti, Kranti; Wang, Gang; Yang, Ence; Cai, James J.

2013-01-01

We present SBEToolbox (Systems Biology and Evolution Toolbox), an open-source Matlab toolbox for biological network analysis. It takes a network file as input, calculates a variety of centralities and topological metrics, clusters nodes into modules, and displays the network using different graph layout algorithms. Straightforward implementation and the inclusion of high-level functions allow the functionality to be easily extended or tailored through developing custom plugins. SBEGUI, a menu-driven graphical user interface (GUI) of SBEToolbox, enables easy access to various network and graph algorithms for programmers and non-programmers alike. All source code and sample data are freely available at https://github.com/biocoder/SBEToolbox/releases. PMID:24027418

SBEToolbox: A Matlab Toolbox for Biological Network Analysis.

PubMed

Konganti, Kranti; Wang, Gang; Yang, Ence; Cai, James J

2013-01-01

We present SBEToolbox (Systems Biology and Evolution Toolbox), an open-source Matlab toolbox for biological network analysis. It takes a network file as input, calculates a variety of centralities and topological metrics, clusters nodes into modules, and displays the network using different graph layout algorithms. Straightforward implementation and the inclusion of high-level functions allow the functionality to be easily extended or tailored through developing custom plugins. SBEGUI, a menu-driven graphical user interface (GUI) of SBEToolbox, enables easy access to various network and graph algorithms for programmers and non-programmers alike. All source code and sample data are freely available at https://github.com/biocoder/SBEToolbox/releases.

SLC9A9 Co-expression modules in autism-associated brain regions.

PubMed

Patak, Jameson; Hess, Jonathan L; Zhang-James, Yanli; Glatt, Stephen J; Faraone, Stephen V

2017-03-01

SLC9A9 is a sodium hydrogen exchanger present in the recycling endosome and highly expressed in the brain. It is implicated in neuropsychiatric disorders, including autism spectrum disorders (ASDs). Little research concerning its gene expression patterns and biological pathways has been conducted. We sought to investigate its possible biological roles in autism-associated brain regions throughout development. We conducted a weighted gene co-expression network analysis on RNA-seq data downloaded from Brainspan. We compared prenatal and postnatal gene expression networks for three ASD-associated brain regions known to have high SLC9A9 gene expression. We also performed an ASD-associated single nucleotide polymorphism enrichment analysis and a cell signature enrichment analysis. The modules showed differences in gene constituents (membership), gene number, and connectivity throughout time. SLC9A9 was highly associated with immune system functions, metabolism, apoptosis, endocytosis, and signaling cascades. Gene list comparison with co-immunoprecipitation data was significant for multiple modules. We found a disproportionately high autism risk signal among genes constituting the prenatal hippocampal module. The modules were enriched with astrocyte and oligodendrocyte markers. SLC9A9 is potentially involved in the pathophysiology of ASDs. Our investigation confirmed proposed functions for SLC9A9, such as endocytosis and immune regulation, while also revealing potential roles in mTOR signaling and cell survival.. By providing a concise molecular map and interactions, evidence of cell type and implicated brain regions we hope this will guide future research on SLC9A9. Autism Res 2017, 10: 414-429. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Dual regulation of gene expression mediated by extended MAPK activation and salicylic acid contributes to robust innate immunity in Arabidopsis thaliana.

PubMed

Tsuda, Kenichi; Mine, Akira; Bethke, Gerit; Igarashi, Daisuke; Botanga, Christopher J; Tsuda, Yayoi; Glazebrook, Jane; Sato, Masanao; Katagiri, Fumiaki

2013-01-01

Network robustness is a crucial property of the plant immune signaling network because pathogens are under a strong selection pressure to perturb plant network components to dampen plant immune responses. Nevertheless, modulation of network robustness is an area of network biology that has rarely been explored. While two modes of plant immunity, Effector-Triggered Immunity (ETI) and Pattern-Triggered Immunity (PTI), extensively share signaling machinery, the network output is much more robust against perturbations during ETI than PTI, suggesting modulation of network robustness. Here, we report a molecular mechanism underlying the modulation of the network robustness in Arabidopsis thaliana. The salicylic acid (SA) signaling sector regulates a major portion of the plant immune response and is important in immunity against biotrophic and hemibiotrophic pathogens. In Arabidopsis, SA signaling was required for the proper regulation of the vast majority of SA-responsive genes during PTI. However, during ETI, regulation of most SA-responsive genes, including the canonical SA marker gene PR1, could be controlled by SA-independent mechanisms as well as by SA. The activation of the two immune-related MAPKs, MPK3 and MPK6, persisted for several hours during ETI but less than one hour during PTI. Sustained MAPK activation was sufficient to confer SA-independent regulation of most SA-responsive genes. Furthermore, the MPK3 and SA signaling sectors were compensatory to each other for inhibition of bacterial growth as well as for PR1 expression during ETI. These results indicate that the duration of the MAPK activation is a critical determinant for modulation of robustness of the immune signaling network. Our findings with the plant immune signaling network imply that the robustness level of a biological network can be modulated by the activities of network components.

Novel aquatic modules for bioregenerative life-support systems based on the closed equilibrated biological aquatic system (c.e.b.a.s.)

NASA Astrophysics Data System (ADS)

Bluem, Volker; Paris, Frank

2002-06-01

The closed equilibrated biological aquatic system (C.E.B.A.S) is a man-made aquatic ecosystem which consists of four subcomponents: an aquatic animal habitat, an aquatic plant bioreactor, an ammonia oxidizing bacteria filter and a data acquisition/control unit. It is a precursor for different types of fish and aquatic plant production sites which are disposed for the integration into bioregenerative life-support systems. The results of two successful spaceflights of a miniaturized C.E.B.A.S version (the C.E.B.A.S. MINI MODULE) allow the optimization of aquatic food production systems which are already developed in the ground laboratory and open new aspects for their utilization as aquatic modules in space bioregenerative life support systems. The total disposition offers different stages of complexity of such aquatic modules starting with simple but efficient aquatic plant cultivators which can be implemented into water recycling systems and ending up in combined plant/fish aquaculture in connection with reproduction modules and hydroponics applications for higher land plants. In principle, aquaculture of fishes and/or other aquatic animals edible for humans offers optimal animal protein production under lowered gravity conditions without the tremendous waste management problems connected with tetrapod breeding and maintenance. The paper presents details of conducted experimental work and of future dispositions which demonstrate clearly that aquaculture is an additional possibility to combine efficient and simple food production in space with water recycling utilizing safe and performable biotechnologies. Moreover, it explains how these systems may contribute to more variable diets to fulfill the needs of multicultural crews.

WGCNA: an R package for weighted correlation network analysis.

PubMed

Langfelder, Peter; Horvath, Steve

2008-12-29

Correlation networks are increasingly being used in bioinformatics applications. For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples. Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures. Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets. These methods have been successfully applied in various biological contexts, e.g. cancer, mouse genetics, yeast genetics, and analysis of brain imaging data. While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial. The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis. The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software. Along with the R package we also present R software tutorials. While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings. The WGCNA package provides R functions for weighted correlation network analysis, e.g. co-expression network analysis of gene expression data. The R package along with its source code and additional material are freely available at http://www.genetics.ucla.edu/labs/horvath/CoexpressionNetwork/Rpackages/WGCNA.

WGCNA: an R package for weighted correlation network analysis

PubMed Central

Langfelder, Peter; Horvath, Steve

2008-01-01

Background Correlation networks are increasingly being used in bioinformatics applications. For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples. Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures. Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets. These methods have been successfully applied in various biological contexts, e.g. cancer, mouse genetics, yeast genetics, and analysis of brain imaging data. While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial. Results The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis. The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software. Along with the R package we also present R software tutorials. While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings. Conclusion The WGCNA package provides R functions for weighted correlation network analysis, e.g. co-expression network analysis of gene expression data. The R package along with its source code and additional material are freely available at . PMID:19114008

The relative vertex clustering value - a new criterion for the fast discovery of functional modules in protein interaction networks

PubMed Central

2015-01-01

Background Cellular processes are known to be modular and are realized by groups of proteins implicated in common biological functions. Such groups of proteins are called functional modules, and many community detection methods have been devised for their discovery from protein interaction networks (PINs) data. In current agglomerative clustering approaches, vertices with just a very few neighbors are often classified as separate clusters, which does not make sense biologically. Also, a major limitation of agglomerative techniques is that their computational efficiency do not scale well to large PINs. Finally, PIN data obtained from large scale experiments generally contain many false positives, and this makes it hard for agglomerative clustering methods to find the correct clusters, since they are known to be sensitive to noisy data. Results We propose a local similarity premetric, the relative vertex clustering value, as a new criterion allowing to decide when a node can be added to a given node's cluster and which addresses the above three issues. Based on this criterion, we introduce a novel and very fast agglomerative clustering technique, FAC-PIN, for discovering functional modules and protein complexes from a PIN data. Conclusions Our proposed FAC-PIN algorithm is applied to nine PIN data from eight different species including the yeast PIN, and the identified functional modules are validated using Gene Ontology (GO) annotations from DAVID Bioinformatics Resources. Identified protein complexes are also validated using experimentally verified complexes. Computational results show that FAC-PIN can discover functional modules or protein complexes from PINs more accurately and more efficiently than HC-PIN and CNM, the current state-of-the-art approaches for clustering PINs in an agglomerative manner. PMID:25734691

Optical Quantification of Harmonic Acoustic Radiation Force Excitation in a Tissue-Mimicking Phantom.

PubMed

Suomi, Visa; Edwards, David; Cleveland, Robin

2015-12-01

Optical tracking was used to characterize acoustic radiation force-induced displacements in a tissue-mimicking phantom. Amplitude-modulated 3.3-MHz ultrasound was used to induce acoustic radiation force in the phantom, which was embedded with 10-μm microspheres that were tracked using a microscope objective and high-speed camera. For sine and square amplitude modulation, the harmonic components of the fundamental and second and third harmonic frequencies were measured. The displacement amplitudes were found to increase linearly with acoustic radiation force up to 10 μm, with sine modulation having 19.5% lower peak-to-peak amplitude values than square modulation. Square modulation produced almost no second harmonic, but energy was present in the third harmonic. For the sine modulation, energy was present in the second harmonic and low energy in the third harmonic. A finite-element model was used to simulate the deformation and was both qualitatively and quantitatively in agreement with the measurements. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Identification of Crowding Stress Tolerance Co-Expression Networks Involved in Sweet Corn Yield

PubMed Central

Choe, Eunsoo; Drnevich, Jenny; Williams, Martin M.

2016-01-01

Tolerance to crowding stress has played a crucial role in improving agronomic productivity in field corn; however, commercial sweet corn hybrids vary greatly in crowding stress tolerance. The objectives were to 1) explore transcriptional changes among sweet corn hybrids with differential yield under crowding stress, 2) identify relationships between phenotypic responses and gene expression patterns, and 3) identify groups of genes associated with yield and crowding stress tolerance. Under conditions of crowding stress, three high-yielding and three low-yielding sweet corn hybrids were grouped for transcriptional and phenotypic analyses. Transcriptional analyses identified from 372 to 859 common differentially expressed genes (DEGs) for each hybrid. Large gene expression pattern variation among hybrids and only 26 common DEGs across all hybrid comparisons were identified, suggesting each hybrid has a unique response to crowding stress. Over-represented biological functions of DEGs also differed among hybrids. Strong correlation was observed between: 1) modules with up-regulation in high-yielding hybrids and yield traits, and 2) modules with up-regulation in low-yielding hybrids and plant/ear traits. Modules linked with yield traits may be important crowding stress response mechanisms influencing crop yield. Functional analysis of the modules and common DEGs identified candidate crowding stress tolerant processes in photosynthesis, glycolysis, cell wall, carbohydrate/nitrogen metabolic process, chromatin, and transcription regulation. Moreover, these biological functions were greatly inter-connected, indicating the importance of improving the mechanisms as a network. PMID:26796516

A statistical framework for biomedical literature mining.

PubMed

Chung, Dongjun; Lawson, Andrew; Zheng, W Jim

2017-09-30

In systems biology, it is of great interest to identify new genes that were not previously reported to be associated with biological pathways related to various functions and diseases. Identification of these new pathway-modulating genes does not only promote understanding of pathway regulation mechanisms but also allow identification of novel targets for therapeutics. Recently, biomedical literature has been considered as a valuable resource to investigate pathway-modulating genes. While the majority of currently available approaches are based on the co-occurrence of genes within an abstract, it has been reported that these approaches show only sub-optimal performances because 70% of abstracts contain information only for a single gene. To overcome such limitation, we propose a novel statistical framework based on the concept of ontology fingerprint that uses gene ontology to extract information from large biomedical literature data. The proposed framework simultaneously identifies pathway-modulating genes and facilitates interpreting functions of these new genes. We also propose a computationally efficient posterior inference procedure based on Metropolis-Hastings within Gibbs sampler for parameter updates and the poor man's reversible jump Markov chain Monte Carlo approach for model selection. We evaluate the proposed statistical framework with simulation studies, experimental validation, and an application to studies of pathway-modulating genes in yeast. The R implementation of the proposed model is currently available at https://dongjunchung.github.io/bayesGO/. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Impact of Cigarette Smoke on the Human and Mouse Lungs: A Gene-Expression Comparison Study

PubMed Central

Morissette, Mathieu C.; Lamontagne, Maxime; Bérubé, Jean-Christophe; Gaschler, Gordon; Williams, Andrew; Yauk, Carole; Couture, Christian; Laviolette, Michel; Hogg, James C.; Timens, Wim; Halappanavar, Sabina; Stampfli, Martin R.; Bossé, Yohan

2014-01-01

Cigarette smoke is well known for its adverse effects on human health, especially on the lungs. Basic research is essential to identify the mechanisms involved in the development of cigarette smoke-related diseases, but translation of new findings from pre-clinical models to the clinic remains difficult. In the present study, we aimed at comparing the gene expression signature between the lungs of human smokers and mice exposed to cigarette smoke to identify the similarities and differences. Using human and mouse whole-genome gene expression arrays, changes in gene expression, signaling pathways and biological functions were assessed. We found that genes significantly modulated by cigarette smoke in humans were enriched for genes modulated by cigarette smoke in mice, suggesting a similar response of both species. Sixteen smoking-induced genes were in common between humans and mice including six newly reported to be modulated by cigarette smoke. In addition, we identified a new conserved pulmonary response to cigarette smoke in the induction of phospholipid metabolism/degradation pathways. Finally, the majority of biological functions modulated by cigarette smoke in humans were also affected in mice. Altogether, the present study provides information on similarities and differences in lung gene expression response to cigarette smoke that exist between human and mouse. Our results foster the idea that animal models should be used to study the involvement of pathways rather than single genes in human diseases. PMID:24663285

Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing

PubMed Central

Gameiro, Sofia R.; Jammed, Momodou L.; Wattenberg, Max M.; Tsang, Kwong Y.; Ferrone, Soldano; Hodge, James W.

2014-01-01

Radiation therapy (RT) is used for local tumor control through direct killing of tumor cells. Radiation-induced cell death can trigger tumor antigen-specific immune responses, but these are often noncurative. Radiation has been demonstrated to induce immunogenic modulation (IM) in various tumor types by altering the biology of surviving cells to render them more susceptible to T cell-mediated killing. Little is known about the mechanism(s) underlying IM elicited by sub-lethal radiation dosing. We have examined the molecular and immunogenic consequences of radiation exposure in breast, lung, and prostate human carcinoma cells. Radiation induced secretion of ATP and HMGB1 in both dying and surviving tumor cells. In vitro and in vivo tumor irradiation induced significant upregulation of multiple components of the antigen-processing machinery and calreticulin cell-surface expression. Augmented CTL lysis specific for several tumor-associated antigens was largely dictated by the presence of calreticulin on the surface of tumor cells and constituted an adaptive response to endoplasmic reticulum stress, mediated by activation of the unfolded protein response. This study provides evidence that radiation induces a continuum of immunogenic alterations in tumor biology, from immunogenic modulation to immunogenic cell death. We also expand the concept of immunogenic modulation, where surviving tumor cells recovering from radiation-induced endoplasmic reticulum stress become more sensitive to CTL killing. These observations offer a rationale for the combined use of radiation with immunotherapy, including for patients failing RT alone. PMID:24480782

Study the effects of varying interference upon the optical properties of turbid samples using NIR spatial light modulation

NASA Astrophysics Data System (ADS)

Shaul, Oren; Fanrazi-Kahana, Michal; Meitav, Omri; Pinhasi, Gad A.; Abookasis, David

2018-03-01

Optical properties of biological tissues are valuable diagnostic parameters which can provide necessary information regarding tissue state during disease pathogenesis and therapy. However, different sources of interference, such as temperature changes may modify these properties, introducing confounding factors and artifacts to data, consequently skewing their interpretation and misinforming clinical decision-making. In the current study, we apply spatial light modulation, a type of diffuse reflectance hyperspectral imaging technique, to monitor the variation in optical properties of highly scattering turbid media in the presence varying levels of the following sources of interference: scattering concentration, temperature, and pressure. Spatial near-infrared (NIR) light modulation is a wide-field, non-contact emerging optical imaging platform capable of separating the effects of tissue scattering from those of absorption, thereby accurately estimating both parameters. With this technique, periodic NIR illumination patterns at alternately low and high spatial frequencies, at six discrete wavelengths between 690 to 970 nm, were sequentially projected upon the medium while a CCD camera collects the diffusely reflected light. Data analysis based assumptions is then performed off-line to recover the medium's optical properties. We conducted a series of experiments demonstrating the changes in absorption and reduced scattering coefficients of commercially available fresh milk and chicken breast tissue under different interference conditions. In addition, information on the refractive index was study under increased pressure. This work demonstrates the utility of NIR spatial light modulation to detect varying sources of interference upon the optical properties of biological samples.

Reusable Reentry Satellite (RRS) system design study: System cost estimates document

NASA Technical Reports Server (NTRS)

1991-01-01

The Reusable Reentry Satellite (RRS) program was initiated to provide life science investigators relatively inexpensive, frequent access to space for extended periods of time with eventual satellite recovery on earth. The RRS will provide an on-orbit laboratory for research on biological and material processes, be launched from a number of expendable launch vehicles, and operate in Low-Altitude Earth Orbit (LEO) as a free-flying unmanned laboratory. SAIC's design will provide independent atmospheric reentry and soft landing in the continental U.S., orbit for a maximum of 60 days, and will sustain three flights per year for 10 years. The Reusable Reentry Vehicle (RRV) will be 3-axis stabilized with artificial gravity up to 1.5g's, be rugged and easily maintainable, and have a modular design to accommodate a satellite bus and separate modular payloads (e.g., rodent module, general biological module, ESA microgravity botany facility, general botany module). The purpose of this System Cost Estimate Document is to provide a Life Cycle Cost Estimate (LCCE) for a NASA RRS Program using SAIC's RRS design. The estimate includes development, procurement, and 10 years of operations and support (O&S) costs for NASA's RRS program. The estimate does not include costs for other agencies which may track or interface with the RRS program (e.g., Air Force tracking agencies or individual RRS experimenters involved with special payload modules (PM's)). The life cycle cost estimate extends over the 10 year operation and support period FY99-2008.

Safety assessment of immunomodulatory biologics: the promise and challenges of regulatory T-cell modulation.

PubMed

Ponce, Rafael A

2011-01-01

Regulatory T-cell (T(reg)) modulation is developing as an important therapeutic opportunity for the treatment of a number of important diseases, including cancer, autoimmunity, infection, and organ transplant rejection. However, as demonstrated with IL-2 and TGN-1412, our understanding of the complex immunological interactions that occur with T(reg) modulation in both non-clinical models and in patients remains limited and appears highly contextual. This lack of understanding will challenge our ability to identify the patient population who might derive the highest benefit from T(reg) modulation and creates special challenges as we transition these therapeutics from non-clinical models into humans. Thus, in vivo testing in the most representative animal model systems, with careful progress in the clinic, will remain critical in developing therapeutics targeting T(reg) and understanding their clinical utility. Moreover, toxicology models can inform some of the potential liabilities associated with T(reg) modulation, but not all, suggesting a continued need to explore and validate predictive models.

Evolutionary and Developmental Modules

PubMed Central

Lacquaniti, Francesco; Ivanenko, Yuri P.; d’Avella, Andrea; Zelik, Karl E.; Zago, Myrka

2013-01-01

The identification of biological modules at the systems level often follows top-down decomposition of a task goal, or bottom-up decomposition of multidimensional data arrays into basic elements or patterns representing shared features. These approaches traditionally have been applied to mature, fully developed systems. Here we review some results from two other perspectives on modularity, namely the developmental and evolutionary perspective. There is growing evidence that modular units of development were highly preserved and recombined during evolution. We first consider a few examples of modules well identifiable from morphology. Next we consider the more difficult issue of identifying functional developmental modules. We dwell especially on modular control of locomotion to argue that the building blocks used to construct different locomotor behaviors are similar across several animal species, presumably related to ancestral neural networks of command. A recurrent theme from comparative studies is that the developmental addition of new premotor modules underlies the postnatal acquisition and refinement of several different motor behaviors in vertebrates. PMID:23730285

Modulator Dynamics Shape the Design Space for Stepwise-Elution Simulated Moving Bed Chromatographic Separations.

PubMed

Wayne, Chris J; Velayudhan, Ajoy

2018-03-31

For proteins and other biological macromolecules, SMB chromatography is best operated non-isocratically. However, traditional modes of non-isocratic SMB operation generate significant mobile-phase modulator dynamics. The mechanisms by which these modulator dynamics affect a separation's success, and thus frame the design space, have yet to be explained quantitatively. Here, the dynamics of the modulator (e.g., salts in ion exchange and hydrophobic interaction chromatography) are explicitly accounted for. This leads to the elucidation of two new design constraints, presented as dimensionless numbers, which quantify the effects of the modulator phenomena and thus predict the success of a non-isocratic SMB separation. Consequently, these two new design constraints re-define the SMB design space. Computational and experimental studies at the boundaries of this design space corroborate the theoretical predictions. The design of efficient and robust operating conditions through use of the new design space is also demonstrated. © 2018 The Authors. Biotechnology Journal Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evolutionary and developmental modules.

PubMed

Lacquaniti, Francesco; Ivanenko, Yuri P; d'Avella, Andrea; Zelik, Karl E; Zago, Myrka

2013-01-01

The identification of biological modules at the systems level often follows top-down decomposition of a task goal, or bottom-up decomposition of multidimensional data arrays into basic elements or patterns representing shared features. These approaches traditionally have been applied to mature, fully developed systems. Here we review some results from two other perspectives on modularity, namely the developmental and evolutionary perspective. There is growing evidence that modular units of development were highly preserved and recombined during evolution. We first consider a few examples of modules well identifiable from morphology. Next we consider the more difficult issue of identifying functional developmental modules. We dwell especially on modular control of locomotion to argue that the building blocks used to construct different locomotor behaviors are similar across several animal species, presumably related to ancestral neural networks of command. A recurrent theme from comparative studies is that the developmental addition of new premotor modules underlies the postnatal acquisition and refinement of several different motor behaviors in vertebrates.

Redox Modulations, Antioxidants, and Neuropsychiatric Disorders

PubMed Central

Fraunberger, Erik A.; Laliberté, Victoria L. M.; Duong, Angela; Andreazza, Ana C.

2016-01-01

Although antioxidants, redox modulations, and neuropsychiatric disorders have been widely studied for many years, the field would benefit from an integrative and corroborative review. Our primary objective is to delineate the biological significance of compounds that modulate our redox status (i.e., reactive species and antioxidants) as well as outline their current role in brain health and the impact of redox modulations on the severity of illnesses. Therefore, this review will not enter into the debate regarding the perceived medical legitimacy of antioxidants but rather seek to clarify their abilities and limitations. With this in mind, antioxidants may be interpreted as natural products with significant pharmacological actions in the body. A renewed understanding of these often overlooked compounds will allow us to critically appraise the current literature and provide an informed, novel perspective on an important healthcare issue. In this review, we will introduce the complex topics of redox modulations and their role in the development of select neuropsychiatric disorders. PMID:26640614

Nonlinear Focal Modulation Microscopy.

PubMed

Zhao, Guangyuan; Zheng, Cheng; Kuang, Cuifang; Zhou, Renjie; Kabir, Mohammad M; Toussaint, Kimani C; Wang, Wensheng; Xu, Liang; Li, Haifeng; Xiu, Peng; Liu, Xu

2018-05-11

We demonstrate nonlinear focal modulation microscopy (NFOMM) to achieve superresolution imaging. Traditional approaches to superresolution that utilize point scanning often rely on spatially reducing the size of the emission pattern by directly narrowing (e.g., through minimizing the detection pinhole in Airyscan, Zeiss) or indirectly peeling its outer profiles [e.g., through depleting the outer emission region in stimulated emission depletion (STED) microscopy]. We show that an alternative conceptualization that focuses on maximizing the optical system's frequency shifting ability offers advantages in further improving resolution while reducing system complexity. In NFOMM, a spatial light modulator and a suitably intense laser illumination are used to implement nonlinear focal-field modulation to achieve a transverse spatial resolution of ∼60  nm (∼λ/10). We show that NFOMM is comparable with STED microscopy and suitable for fundamental biology studies, as evidenced in imaging nuclear pore complexes, tubulin and vimentin in Vero cells. Since NFOMM is readily implemented as an add-on module to a laser-scanning microscope, we anticipate wide utility of this new imaging technique.

Nonlinear Focal Modulation Microscopy

NASA Astrophysics Data System (ADS)

Zhao, Guangyuan; Zheng, Cheng; Kuang, Cuifang; Zhou, Renjie; Kabir, Mohammad M.; Toussaint, Kimani C.; Wang, Wensheng; Xu, Liang; Li, Haifeng; Xiu, Peng; Liu, Xu

2018-05-01

We demonstrate nonlinear focal modulation microscopy (NFOMM) to achieve superresolution imaging. Traditional approaches to superresolution that utilize point scanning often rely on spatially reducing the size of the emission pattern by directly narrowing (e.g., through minimizing the detection pinhole in Airyscan, Zeiss) or indirectly peeling its outer profiles [e.g., through depleting the outer emission region in stimulated emission depletion (STED) microscopy]. We show that an alternative conceptualization that focuses on maximizing the optical system's frequency shifting ability offers advantages in further improving resolution while reducing system complexity. In NFOMM, a spatial light modulator and a suitably intense laser illumination are used to implement nonlinear focal-field modulation to achieve a transverse spatial resolution of ˜60 nm (˜λ /10 ). We show that NFOMM is comparable with STED microscopy and suitable for fundamental biology studies, as evidenced in imaging nuclear pore complexes, tubulin and vimentin in Vero cells. Since NFOMM is readily implemented as an add-on module to a laser-scanning microscope, we anticipate wide utility of this new imaging technique.

Je pense donc je fais: transcranial direct current stimulation modulates brain oscillations associated with motor imagery and movement observation.

PubMed

Lapenta, Olivia M; Minati, Ludovico; Fregni, Felipe; Boggio, Paulo S

2013-01-01

Motor system neural networks are activated during movement imagery, observation and execution, with a neural signature characterized by suppression of the Mu rhythm. In order to investigate the origin of this neurophysiological marker, we tested whether transcranial direct current stimulation (tDCS) modifies Mu rhythm oscillations during tasks involving observation and imagery of biological and non-biological movements. We applied tDCS (anodal, cathodal, and sham) in 21 male participants (mean age 23.8 ± 3.06), over the left M1 with a current of 2 mA for 20 min. Following this, we recorded the EEG at C3, C4, and Cz and surrounding C3 and C4 electrodes. Analyses of C3 and C4 showed significant effects for biological vs. non-biological movement (p = 0.005), and differential hemisphere effects according to the type of stimulation (p = 0.04) and type of movement (p = 0.02). Analyses of surrounding electrodes revealed significant interaction effects considering type of stimulation and imagery or observation of biological or non-biological movement (p = 0.03). The main findings of this study were (1) Mu desynchronization during biological movement of the hand region in the contralateral hemisphere after sham tDCS; (2) polarity-dependent modulation effects of tDCS on the Mu rhythm, i.e., anodal tDCS led to Mu synchronization while cathodal tDCS led to Mu desynchronization during movement observation and imagery (3) specific focal and opposite inter-hemispheric effects, i.e., contrary effects for the surrounding electrodes during imagery condition and also for inter-hemispheric electrodes (C3 vs. C4). These findings provide insights into the cortical oscillations during movement observation and imagery. Furthermore, it shows that tDCS can be highly focal when guided by a behavioral task.

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

Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.

Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of thismore » novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for small–tumor target patients. This optimizer will be used in an upcoming feasibility trial on LET{sub d} painting for radioresistant tumors.« less

Wnt signal transduction pathways: modules, development and evolution.

PubMed

Nayak, Losiana; Bhattacharyya, Nitai P; De, Rajat K

2016-08-01

Wnt signal transduction pathway (Wnt STP) is a crucial intracellular pathway mainly due to its participation in important biological processes, functions, and diseases, i.e., embryonic development, stem-cell management, and human cancers among others. This is why Wnt STP is one of the highest researched signal transduction pathways. Study and analysis of its origin, expansion and gradual development to the present state as found in humans is one aspect of Wnt research. The pattern of development and evolution of the Wnt STP among various species is not clear till date. A phylogenetic tree created from Wnt STPs of multiple species may address this issue. In this respect, we construct a phylogenetic tree from modules of Wnt STPs of diverse species. We term it as the 'Module Tree'. A module is nothing but a self-sufficient minimally-dependent subset of the original Wnt STP. Authenticity of the module tree is tested by comparing it with the two reference trees. The module tree performs better than an alternative phylogenetic tree constructed from pathway topology of Wnt STPs. Moreover, an evolutionary emergence pattern of the Wnt gene family is created and the module tree is tallied with it to showcase the significant resemblances.

Microarray and network-based identification of functional modules and pathways of active tuberculosis.

PubMed

Bian, Zhong-Rui; Yin, Juan; Sun, Wen; Lin, Dian-Jie

2017-04-01

Diagnose of active tuberculosis (TB) is challenging and treatment response is also difficult to efficiently monitor. The aim of this study was to use an integrated analysis of microarray and network-based method to the samples from publically available datasets to obtain a diagnostic module set and pathways in active TB. Towards this goal, background protein-protein interactions (PPI) network was generated based on global PPI information and gene expression data, following by identification of differential expression network (DEN) from the background PPI network. Then, ego genes were extracted according to the degree features in DEN. Next, module collection was conducted by ego gene expansion based on EgoNet algorithm. After that, differential expression of modules between active TB and controls was evaluated using random permutation test. Finally, biological significance of differential modules was detected by pathways enrichment analysis based on Reactome database, and Fisher's exact test was implemented to extract differential pathways for active TB. Totally, 47 ego genes and 47 candidate modules were identified from the DEN. By setting the cutoff-criteria of gene size >5 and classification accuracy ≥0.9, 7 ego modules (Module 4, Module 7, Module 9, Module 19, Module 25, Module 38 and Module 43) were extracted, and all of them had the statistical significance between active TB and controls. Then, Fisher's exact test was conducted to capture differential pathways for active TB. Interestingly, genes in Module 4, Module 25, Module 38, and Module 43 were enriched in the same pathway, formation of a pool of free 40S subunits. Significant pathway for Module 7 and Module 9 was eukaryotic translation termination, and for Module 19 was nonsense mediated decay enhanced by the exon junction complex (EJC). Accordingly, differential modules and pathways might be potential biomarkers for treating active TB, and provide valuable clues for better understanding of molecular mechanism of active TB. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nanobodies and recombinant binders in cell biology

PubMed Central

Helma, Jonas; Cardoso, M. Cristina; Muyldermans, Serge

2015-01-01

Antibodies are key reagents to investigate cellular processes. The development of recombinant antibodies and binders derived from natural protein scaffolds has expanded traditional applications, such as immunofluorescence, binding arrays, and immunoprecipitation. In addition, their small size and high stability in ectopic environments have enabled their use in all areas of cell research, including structural biology, advanced microscopy, and intracellular expression. Understanding these novel reagents as genetic modules that can be integrated into cellular pathways opens up a broad experimental spectrum to monitor and manipulate cellular processes. PMID:26056137

Vaporous Hydrogen Peroxide (VHP) Decontamination of a C-141B Starlifter Aircraft: Validation of VHP and Modified VHP (mVHP) Fumigation Decontamination Process via VHP-Sensor, Biological Indicator, and HD Simulant in a Large-Scale Environment

DTIC Science & Technology

2007-03-01

Geobacillus stearothermophilus biological indicator (BI) strips and coupons of three aircraft related surface materials contaminated with the same type...Starlifter Aircraft BIs Geobacillus stearothermophilus mVHP system Vaporizer modules Coupons HD Ammonia Computational flow dynamics CARC CEPS 16. SECURITY...21 18. G. stearothermophilus ATCC 7953VHP Exposure Test Results ..................... 33 19. Vapor Cup

Observation Platform for Dynamic Biomedical and Biotechnology Experiments Using the International Space Station (ISS) Light Microscopy Module (LMM)

NASA Technical Reports Server (NTRS)

Kurk, Michael A. (Andy)

2015-01-01

Techshot, Inc., has developed an observation platform for the LMM on the ISS that will enable biomedical and biotechnology experiments. The LMM Dynamic Stage consists of an electronics module and the first two of a planned suite of experiment modules. Specimens and reagent solutions can be injected into a small, hollow microscope slide-the heart of the innovation-via a combination of small reservoirs, pumps, and valves. A life science experiment module allows investigators to load up to two different fluids for on-orbit, real-time image cytometry. Fluids can be changed to initiate a process, fix biological samples, or retrieve suspended cells. A colloid science experiment module conducts microparticle and nanoparticle tests for investigation of colloid self-assembly phenomena. This module includes a hollow glass slide and heating elements for the creation of a thermal gradient from one end of the slide to the other. The electronics module supports both experiment modules and contains a unique illuminator/condenser for bright and dark field and phase contrast illumination, power supplies for two piezoelectric pumps, and controller boards for pumps and valves. This observation platform safely contains internal fluids and will greatly accelerate the research and development (R&D) cycle of numerous experiments, products, and services aboard the ISS.

Entropy-based divergent and convergent modular pattern reveals additive and synergistic anticerebral ischemia mechanisms

PubMed Central

Yu, Yanan; Zhang, Xiaoxu; Li, Bing; Zhang, Yingying; Liu, Jun; Li, Haixia; Chen, Yinying; Wang, Pengqian; Kang, Ruixia; Wu, Hongli

2016-01-01

Module-based network analysis of diverse pharmacological mechanisms is critical to systematically understand combination therapies and disease outcomes. We first constructed drug-target ischemic networks in baicalin, jasminoidin, ursodeoxycholic acid, and their combinations baicalin and jasminoidin as well as jasminoidin and ursodeoxycholic acid groups and identified modules using the entropy-based clustering algorithm. The modules 11, 7, 4, 8 and 3 were identified as baicalin, jasminoidin, ursodeoxycholic acid, baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid-emerged responsive modules, while 12, 8, 15, 17 and 9 were identified as disappeared responsive modules based on variation of topological similarity, respectively. No overlapping differential biological processes were enriched between baicalin and jasminoidin and jasminoidin and ursodeoxycholic acid pure emerged responsive modules, but two were enriched by their co-disappeared responsive modules including nucleotide-excision repair and epithelial structure maintenance. We found an additive effect of baicalin and jasminoidin in a divergent pattern and a synergistic effect of jasminoidin and ursodeoxycholic acid in a convergent pattern on “central hit strategy” of regulating inflammation against cerebral ischemia. The proposed module-based approach may provide us a holistic view to understand multiple pharmacological mechanisms associated with differential phenotypes from the standpoint of modular pharmacology. PMID:27480252

Biomaterials-Based Electronics: Polymers and Interfaces for Biology and Medicine

PubMed Central

Muskovich, Meredith; Bettinger, Christopher J.

2012-01-01

Advanced polymeric biomaterials continue to serve as a cornerstone of new medical technologies and therapies. The vast majority of these materials, both natural and synthetic, interact with biological matter without direct electronic communication. However, biological systems have evolved to synthesize and employ naturally-derived materials for the generation and modulation of electrical potentials, voltage gradients, and ion flows. Bioelectric phenomena can be interpreted as potent signaling cues for intra- and inter-cellular communication. These cues can serve as a gateway to link synthetic devices with biological systems. This progress report will provide an update on advances in the application of electronically active biomaterials for use in organic electronics and bio-interfaces. Specific focus will be granted to the use of natural and synthetic biological materials as integral components in technologies such as thin film electronics, in vitro cell culture models, and implantable medical devices. Future perspectives and emerging challenges will also be highlighted. PMID:23184740

The Future of Biologic Coatings for Orthopaedic Implants

PubMed Central

Goodman, Stuart B.; Yao, Zhenyu; Keeney, Michael; Yang, Fan

2013-01-01

Implants are widely used for othopaedic applications such as fixing fractures, repairing nonunions, obtaining a joint arthrodesis, total joint arthroplasty, spinal reconstruction, and soft tissue anchorage. Previously, orthopaedic implants were designed simply as mechanical devices; the biological aspects of the implant were a byproduct of stable internal/external fixation of the device to the surrounding bone or soft tissue. More recently, biologic coatings have been incorporated into orthopaedic implants in order to modulate the surrounding biological environment. This opinion article reviews current and potential future use of biologic coatings for orthopaedic implants to facilitate osseointegration and mitigate possible adverse tissue responses including the foreign body reaction and implant infection. While many of these coatings are still in the preclinical testing stage, bioengineers, material scientists and surgeons continue to explore surface coatings as a means of improving clinical outcome of patients undergoing orthopaedic surgery. PMID:23391496

EcoFlex: A Multifunctional MoClo Kit for E. coli Synthetic Biology.

PubMed

Lai, Hung-En; Moore, Simon; Polizzi, Karen; Freemont, Paul

2018-01-01

Development of advanced synthetic biology tools is always in demand since they act as a platform technology to enable rapid prototyping of biological constructs in a high-throughput manner. EcoFlex is a modular cloning (MoClo) kit for Escherichia coli and is based on the Golden Gate principles, whereby Type IIS restriction enzymes (BsaI, BsmBI, BpiI) are used to construct modular genetic elements (biological parts) in a bottom-up approach. Here, we describe a collection of plasmids that stores various biological parts including promoters, RBSs, terminators, ORFs, and destination vectors, each encoding compatible overhangs allowing hierarchical assembly into single transcription units or a full-length polycistronic operon or biosynthetic pathway. A secondary module cloning site is also available for pathway optimization, in order to limit library size if necessary. Here, we show the utility of EcoFlex using the violacein biosynthesis pathway as an example.

Modularization of genetic elements promotes synthetic metabolic engineering.

PubMed

Qi, Hao; Li, Bing-Zhi; Zhang, Wen-Qian; Liu, Duo; Yuan, Ying-Jin

2015-11-15

In the context of emerging synthetic biology, metabolic engineering is moving to the next stage powered by new technologies. Systematical modularization of genetic elements makes it more convenient to engineer biological systems for chemical production or other desired purposes. In the past few years, progresses were made in engineering metabolic pathway using synthetic biology tools. Here, we spotlighted the topic of implementation of modularized genetic elements in metabolic engineering. First, we overviewed the principle developed for modularizing genetic elements and then discussed how the genetic modules advanced metabolic engineering studies. Next, we picked up some milestones of engineered metabolic pathway achieved in the past few years. Last, we discussed the rapid raised synthetic biology field of "building a genome" and the potential in metabolic engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Biological hydrogels as selective diffusion barriers.

PubMed

Lieleg, Oliver; Ribbeck, Katharina

2011-09-01

The controlled exchange of molecules between organelles, cells, or organisms and their environment is crucial for life. Biological gels such as mucus, the extracellular matrix (ECM), and the biopolymer barrier within the nuclear pore are well suited to achieve such a selective exchange, allowing passage of particular molecules while rejecting many others. Although hydrogel-based filters are integral parts of biology, clear concepts of how their barrier function is controlled at a microscopic level are still missing. We summarize here our current understanding of how selective filtering is established by different biopolymer-based hydrogels. We ask if the modulation of microscopic particle transport in biological hydrogels is based on a generic filtering principle which employs biochemical/biophysical interactions with the filtered molecules rather than size-exclusion effects. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Biology of Cancer Exosomes: Insights and New Perspectives.

PubMed

Ruivo, Carolina F; Adem, Bárbara; Silva, Miguel; Melo, Sónia A

2017-12-01

Exosomes are a subclass of extracellular vesicles involved in intercellular communication that are released by all cell types, including cancer cells. Cancer exosomes carry malignant information in the form of proteins, lipids, and nucleic acids that can reprogram recipient cells. Exosomes have emerged as putative biological mediators in cancer contributing to major steps of disease progression. A leading role exists for cancer exosomes in specific aspects of tumor progression: modulation of immune response, tumor microenvironment reprogramming, and metastasis. This review will address the functions attributed to cancer exosomes in these three aspects of cancer biology, highlighting recent advances and potential limitations. Finally, we explore alternative strategies to develop better models to study cancer exosomes biology. Cancer Res; 77(23); 6480-8. ©2017 AACR . ©2017 American Association for Cancer Research.

Quantitative High-Throughput Screening and Orthogonal Assays to Identify Modulators of the Vitamin D Receptor (SETAC)

EPA Science Inventory

The Vitamin D nuclear receptor (VDR) is a selective, ligand-inducible transcription factor involved in numerous biological processes such as cell proliferation, differentiation, detoxification, calcium homeostasis, neurodevelopment, immune system regulation, cardiovascular functi...

Toxicogenomic Effects Common to Triazole Antifungals and Conserved Between Rats and Humans

EPA Science Inventory

The triazole antifungals myclobutanil, propiconazole and triadimefon cause varying degrees of hepatic toxicity and disrupt steroid hormone homeostasis in rodent in vivo models. To identify biological pathways consistently modulated across multiple time-points and various study d...

Environmental versatility promotes modularity in genome-scale metabolic networks.

PubMed

Samal, Areejit; Wagner, Andreas; Martin, Olivier C

2011-08-24

The ubiquity of modules in biological networks may result from an evolutionary benefit of a modular organization. For instance, modularity may increase the rate of adaptive evolution, because modules can be easily combined into new arrangements that may benefit their carrier. Conversely, modularity may emerge as a by-product of some trait. We here ask whether this last scenario may play a role in genome-scale metabolic networks that need to sustain life in one or more chemical environments. For such networks, we define a network module as a maximal set of reactions that are fully coupled, i.e., whose fluxes can only vary in fixed proportions. This definition overcomes limitations of purely graph based analyses of metabolism by exploiting the functional links between reactions. We call a metabolic network viable in a given chemical environment if it can synthesize all of an organism's biomass compounds from nutrients in this environment. An organism's metabolism is highly versatile if it can sustain life in many different chemical environments. We here ask whether versatility affects the modularity of metabolic networks. Using recently developed techniques to randomly sample large numbers of viable metabolic networks from a vast space of metabolic networks, we use flux balance analysis to study in silico metabolic networks that differ in their versatility. We find that highly versatile networks are also highly modular. They contain more modules and more reactions that are organized into modules. Most or all reactions in a module are associated with the same biochemical pathways. Modules that arise in highly versatile networks generally involve reactions that process nutrients or closely related chemicals. We also observe that the metabolism of E. coli is significantly more modular than even our most versatile networks. Our work shows that modularity in metabolic networks can be a by-product of functional constraints, e.g., the need to sustain life in multiple environments. This organizational principle is insensitive to the environments we consider and to the number of reactions in a metabolic network. Because we observe this principle not just in one or few biological networks, but in large random samples of networks, we propose that it may be a generic principle of metabolic network organization.

Applied Graph-Mining Algorithms to Study Biomolecular Interaction Networks

PubMed Central

2014-01-01

Protein-protein interaction (PPI) networks carry vital information on the organization of molecular interactions in cellular systems. The identification of functionally relevant modules in PPI networks is one of the most important applications of biological network analysis. Computational analysis is becoming an indispensable tool to understand large-scale biomolecular interaction networks. Several types of computational methods have been developed and employed for the analysis of PPI networks. Of these computational methods, graph comparison and module detection are the two most commonly used strategies. This review summarizes current literature on graph kernel and graph alignment methods for graph comparison strategies, as well as module detection approaches including seed-and-extend, hierarchical clustering, optimization-based, probabilistic, and frequent subgraph methods. Herein, we provide a comprehensive review of the major algorithms employed under each theme, including our recently published frequent subgraph method, for detecting functional modules commonly shared across multiple cancer PPI networks. PMID:24800226

Modular microfluidics for point-of-care protein purifications

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

Millet, L. J.; Lucheon, J. D.; Standaert, R. F.

Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured tomore » suit a variety of fluidic operations or biochemical processes. In conclusion, we demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.« less

Shrink-film microfluidic education modules: Complete devices within minutes

PubMed Central

Nguyen, Diep; McLane, Jolie; Lew, Valerie; Pegan, Jonathan; Khine, Michelle

2011-01-01

As advances in microfluidics continue to make contributions to diagnostics and life sciences, broader awareness of this expanding field becomes necessary. By leveraging low-cost microfabrication techniques that require no capital equipment or infrastructure, simple, accessible, and effective educational modules can be made available for a broad range of educational needs from middle school demonstrations to college laboratory classes. These modules demonstrate key microfluidic concepts such as diffusion and separation as well as “laboratory on-chip” applications including chemical reactions and biological assays. These modules are intended to provide an interdisciplinary hands-on experience, including chip design, fabrication of functional devices, and experiments at the microscale. Consequently, students will be able to conceptualize physics at small scales, gain experience in computer-aided design and microfabrication, and perform experiments—all in the context of addressing real-world challenges by making their own lab-on-chip devices. PMID:21799715

Shrink-film microfluidic education modules: Complete devices within minutes.

PubMed

Nguyen, Diep; McLane, Jolie; Lew, Valerie; Pegan, Jonathan; Khine, Michelle

2011-06-01

As advances in microfluidics continue to make contributions to diagnostics and life sciences, broader awareness of this expanding field becomes necessary. By leveraging low-cost microfabrication techniques that require no capital equipment or infrastructure, simple, accessible, and effective educational modules can be made available for a broad range of educational needs from middle school demonstrations to college laboratory classes. These modules demonstrate key microfluidic concepts such as diffusion and separation as well as "laboratory on-chip" applications including chemical reactions and biological assays. These modules are intended to provide an interdisciplinary hands-on experience, including chip design, fabrication of functional devices, and experiments at the microscale. Consequently, students will be able to conceptualize physics at small scales, gain experience in computer-aided design and microfabrication, and perform experiments-all in the context of addressing real-world challenges by making their own lab-on-chip devices.

Modular microfluidics for point-of-care protein purifications.

PubMed

Millet, L J; Lucheon, J D; Standaert, R F; Retterer, S T; Doktycz, M J

2015-04-21

Biochemical separations are the heart of diagnostic assays and purification methods for biologics. On-chip miniaturization and modularization of separation procedures will enable the development of customized, portable devices for personalized health-care diagnostics and point-of-use production of treatments. In this report, we describe the design and fabrication of miniature ion exchange, size exclusion and affinity chromatography modules for on-chip clean-up of recombinantly-produced proteins. Our results demonstrate that these common separations techniques can be implemented in microfluidic modules with performance comparable to conventional approaches. We introduce embedded 3-D microfluidic interconnects for integrating micro-scale separation modules that can be arranged and reconfigured to suit a variety of fluidic operations or biochemical processes. We demonstrate the utility of the modular approach with a platform for the enrichment of enhanced green fluorescent protein (eGFP) from Escherichia coli lysate through integrated affinity and size-exclusion chromatography modules.

Materials Science Research Rack-1 (MSRR-1)

NASA Technical Reports Server (NTRS)

2001-01-01

This scale model depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Key elements are labeled in other images (0101754, 0101829, 0101830, and TBD). This image is from a digital still camera; higher resolution is not available.

Microgravity

NASA Image and Video Library

2001-06-05

This scale model depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Key elements are labeled in other images (0101754, 0101829, and TBD). This composite is from a digital still camera; higher resolution is not available.

Materials Science Research Rack-1 (MSRR-1)

NASA Technical Reports Server (NTRS)

2001-01-01

This scale model depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Here the transparent furnace is extracted for servicing. Key elements are labeled in other images (0101754, 0101829, 0101830, and TBD).

Microgravity

NASA Image and Video Library

2001-06-05

This scale model depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Key elements are labeled in other images (0101754, 0101829, 0101830, and TBD). This image is from a digital still camera; higher resolution is not available.

Materials Science Research Rack-1 (MSRR-1)

NASA Technical Reports Server (NTRS)

2001-01-01

This scale model depicts the Materials Science Research Rack-1 (MSRR-1) being developed by NASA's Marshall Space Flight Center and the European Space Agency (ESA) for placement in the Destiny laboratory module aboard the International Space Station. The rack is part of the plarned Materials Science Research Facility (MSRF) and is expected to include two furnace module inserts, a Quench Module Insert (being developed by NASA's Marshall Space Flight Center) to study directional solidification in rapidly cooled alloys and a Diffusion Module Insert (being developed by the European Space Agency) to study crystal growth, and a transparent furnace (being developed by NASA's Space Product Development program). Multi-user equipment in the rack is being developed under the auspices of NASA's Office of Biological and Physical Research (OBPR) and ESA. Key elements are labeled in other images (0101754, 0101829, and TBD). This composite is from a digital still camera; higher resolution is not available.

A Low-Cost, Hands-on Module to Characterize Antimicrobial Compounds Using an Interdisciplinary, Biophysical Approach

PubMed Central

Kaushik, Karishma S.; Kessel, Ashley; Ratnayeke, Nalin; Gordon, Vernita D.

2015-01-01

We have developed a hands-on experimental module that combines biology experiments with a physics-based analytical model in order to characterize antimicrobial compounds. To understand antibiotic resistance, participants perform a disc diffusion assay to test the antimicrobial activity of different compounds and then apply a diffusion-based analytical model to gain insights into the behavior of the active antimicrobial component. In our experience, this module was robust, reproducible, and cost-effective, suggesting that it could be implemented in diverse settings such as undergraduate research, STEM (science, technology, engineering, and math) camps, school programs, and laboratory training workshops. By providing valuable interdisciplinary research experience in science outreach and education initiatives, this module addresses the paucity of structured training or education programs that integrate diverse scientific fields. Its low-cost requirements make it especially suitable for use in resource-limited settings. PMID:25602254