396 research outputs found
Creating a Journal Through a Musical Journey
Music has always been an important part of my life. It has helped me through some extremely challenging times. Music has had a profound impact on my feelings, thoughts and moods. I seem to connect with it on a deeper level, which has helped me deal with personal issues that I have endured. Because of the help that I have received from music, based on my own life experiences, I feel that I needed to share this connection with others who may be struggling with life‟s uncertainties as well. Therefore, I will compile a collection of journal entries in which I will listen to different types of music for thirty days. I will reflect primarily on how the music has affected me including thoughts and feelings and memories. I will be sure to use as many different genres as possible in order to get a wide range of reactions. In order to reach out to other people and get feedback on my observations, I will transcribe my journal entries onto a personal web blog, where they can leave feedback and comments. I feel that my journal will be an extremely creative outlet for me and others because of the ability to reflect on the music and how it affects us on a more personal level
Functional cartography of complex metabolic networks
High-throughput techniques are leading to an explosive growth in the size of
biological databases and creating the opportunity to revolutionize our
understanding of life and disease. Interpretation of these data remains,
however, a major scientific challenge. Here, we propose a methodology that
enables us to extract and display information contained in complex networks.
Specifically, we demonstrate that one can (i) find functional modules in
complex networks, and (ii) classify nodes into universal roles according to
their pattern of intra- and inter-module connections. The method thus yields a
``cartographic representation'' of complex networks. Metabolic networks are
among the most challenging biological networks and, arguably, the ones with
more potential for immediate applicability. We use our method to analyze the
metabolic networks of twelve organisms from three different super-kingdoms. We
find that, typically, 80% of the nodes are only connected to other nodes within
their respective modules, and that nodes with different roles are affected by
different evolutionary constraints and pressures. Remarkably, we find that
low-degree metabolites that connect different modules are more conserved than
hubs whose links are mostly within a single module.Comment: 17 pages, 4 figures. Go to http://amaral.northwestern.edu for the PDF
file of the reprin
Multiscale computational analysis of Xenopus laevis morphogenesis reveals key insights of systems-level behavior
<p>Abstract</p> <p>Background</p> <p>Tissue morphogenesis is a complex process whereby tissue structures self-assemble by the aggregate behaviors of independently acting cells responding to both intracellular and extracellular cues in their environment. During embryonic development, morphogenesis is particularly important for organizing cells into tissues, and although key regulatory events of this process are well studied in isolation, a number of important systems-level questions remain unanswered. This is due, in part, to a lack of integrative tools that enable the coupling of biological phenomena across spatial and temporal scales. Here, we present a new computational framework that integrates intracellular signaling information with multi-cell behaviors in the context of a spatially heterogeneous tissue environment.</p> <p>Results</p> <p>We have developed a computational simulation of mesendoderm migration in the <it>Xenopus laevis </it>explant model, which is a well studied biological model of tissue morphogenesis that recapitulates many features of this process during development in humans. The simulation couples, via a JAVA interface, an ordinary differential equation-based mass action kinetics model to compute intracellular Wnt/β-catenin signaling with an agent-based model of mesendoderm migration across a fibronectin extracellular matrix substrate. The emergent cell behaviors in the simulation suggest the following properties of the system: maintaining the integrity of cell-to-cell contact signals is necessary for preventing fractionation of cells as they move, contact with the Fn substrate and the existence of a Fn gradient provides an extracellular feedback loop that governs migration speed, the incorporation of polarity signals is required for cells to migrate in the same direction, and a delicate balance of integrin and cadherin interactions is needed to reproduce experimentally observed migratory behaviors.</p> <p>Conclusion</p> <p>Our computational framework couples two different spatial scales in biology: intracellular with multicellular. In our simulation, events at one scale have quantitative and dynamic impact on events at the other scale. This integration enables the testing and identification of key systems-level hypotheses regarding how signaling proteins affect overall tissue-level behavior during morphogenesis in an experimentally verifiable system. Applications of this approach extend to the study of tissue patterning processes that occur during adulthood and disease, such as tumorgenesis and atherogenesis.</p
The NASA Exoplanet Archive: Data and Tools for Exoplanet Research
We describe the contents and functionality of the NASA Exoplanet Archive, a
database and tool set funded by NASA to support astronomers in the exoplanet
community. The current content of the database includes interactive tables
containing properties of all published exoplanets, Kepler planet candidates,
threshold-crossing events, data validation reports and target stellar
parameters, light curves from the Kepler and CoRoT missions and from several
ground-based surveys, and spectra and radial velocity measurements from the
literature. Tools provided to work with these data include a transit ephemeris
predictor, both for single planets and for observing locations, light curve
viewing and normalization utilities, and a periodogram and phased light curve
service. The archive can be accessed at
http://exoplanetarchive.ipac.caltech.edu.Comment: Accepted for publication in the Publications of the Astronomical
Society of the Pacific, 4 figure
Matrix Rigidity Regulates Cancer Cell Growth by Modulating Cellular Metabolism and Protein Synthesis
Background: Tumor cells in vivo encounter diverse types of microenvironments both at the site of the primary tumor and at sites of distant metastases. Understanding how the various mechanical properties of these microenvironments affect the biology of tumor cells during disease progression is critical in identifying molecular targets for cancer therapy. Methodology/Principal Findings: This study uses flexible polyacrylamide gels as substrates for cell growth in conjunction with a novel proteomic approach to identify the properties of rigidity-dependent cancer cell lines that contribute to their differential growth on soft and rigid substrates. Compared to cells growing on more rigid/stiff substrates (>10,000 Pa), cells on soft substrates (150–300 Pa) exhibited a longer cell cycle, due predominantly to an extension of the G1 phase of the cell cycle, and were metabolically less active, showing decreased levels of intracellular ATP and a marked reduction in protein synthesis. Using stable isotope labeling of amino acids in culture (SILAC) and mass spectrometry, we measured the rates of protein synthesis of over 1200 cellular proteins under growth conditions on soft and rigid/stiff substrates. We identified cellular proteins whose syntheses were either preferentially inhibited or preserved on soft matrices. The former category included proteins that regulate cytoskeletal structures (e.g., tubulins) and glycolysis (e.g., phosphofructokinase-1), whereas the latter category included proteins that regulate key metabolic pathways required for survival, e.g., nicotinamide phosphoribosyltransferase, a regulator of the NAD salvage pathway. Conclusions/Significance: The cellular properties of rigidity-dependent cancer cells growing on soft matrices are reminiscent of the properties of dormant cancer cells, e.g., slow growth rate and reduced metabolism. We suggest that the use of relatively soft gels as cell culture substrates would allow molecular pathways to be studied under conditions that reflect the different mechanical environments encountered by cancer cells upon metastasis to distant sites
Signatures of arithmetic simplicity in metabolic network architecture
Metabolic networks perform some of the most fundamental functions in living
cells, including energy transduction and building block biosynthesis. While
these are the best characterized networks in living systems, understanding
their evolutionary history and complex wiring constitutes one of the most
fascinating open questions in biology, intimately related to the enigma of
life's origin itself. Is the evolution of metabolism subject to general
principles, beyond the unpredictable accumulation of multiple historical
accidents? Here we search for such principles by applying to an artificial
chemical universe some of the methodologies developed for the study of genome
scale models of cellular metabolism. In particular, we use metabolic flux
constraint-based models to exhaustively search for artificial chemistry
pathways that can optimally perform an array of elementary metabolic functions.
Despite the simplicity of the model employed, we find that the ensuing pathways
display a surprisingly rich set of properties, including the existence of
autocatalytic cycles and hierarchical modules, the appearance of universally
preferable metabolites and reactions, and a logarithmic trend of pathway length
as a function of input/output molecule size. Some of these properties can be
derived analytically, borrowing methods previously used in cryptography. In
addition, by mapping biochemical networks onto a simplified carbon atom
reaction backbone, we find that several of the properties predicted by the
artificial chemistry model hold for real metabolic networks. These findings
suggest that optimality principles and arithmetic simplicity might lie beneath
some aspects of biochemical complexity
Anisotropic effect of Cd and Hg doping on Pauli limited superconductor CeCoIn
We investigated the effect of Cd and Hg doping on the first order
superconducting (SC) transition and the high field-low temperature SC state of
CeCoIn by measuring the specific heat of CeCo(InCd) with x=0.0011, 0.0022 and 0.0033 and CeCo(InHg) with x=0.00016, 0.00032, and 0.00048 at temperatures down to 0.1 K and
fields up to 14 T. Cd substitution rapidly suppresses the cross-over
temperature , where the superconducting transition changes from
second to first order, to =0 K with x=0.0022 for [100], while
it remains roughly constant up to x=0.0033 for [001]. The
associated anomaly of the proposed FFLO state in Hg-doped samples is washed out
by x=0.00048, while remaining at the same temperature, indicating high
sensitivity of that state to impurities. We interpret these results as
supporting the non-magnetic, possibly FFLO, origin of the high field - low
temperature state in CeCoIn
In Vivo Gene Essentiality and Metabolism in Bordetella pertussis
Bordetella pertussis is the causative agent of whooping cough, a serious respiratory illness affecting children and adults, associated with prolonged cough and potential mortality. Whooping cough has reemerged in recent years, emphasizing a need for increased knowledge of basic mechanisms of B. pertussis growth and pathogenicity. While previous studies have provided insight into in vitro gene essentiality of this organism, very little is known about in vivo gene essentiality, a critical gap in knowledge, since B. pertussis has no previously identified environmental reservoir and is isolated from human respiratory tract samples. We hypothesize that the metabolic capabilities of B. pertussis are especially tailored to the respiratory tract and that many of the genes involved in B. pertussis metabolism would be required to establish infection in vivo. In this study, we generated a diverse library of transposon mutants and then used it to probe gene essentiality in vivo in a murine model of infection. Using the CON-ARTIST pipeline, 117 genes were identified as conditionally essential at 1 day postinfection, and 169 genes were identified as conditionally essential at 3 days postinfection. Most of the identified genes were associated with metabolism, and we utilized two existing genome-scale metabolic network reconstructions to probe the effects of individual essential genes on biomass synthesis. This analysis suggested a critical role for glucose metabolism and lipooligosaccharide biosynthesis in vivo. This is the first genome-wide evaluation of in vivo gene essentiality in B. pertussis and provides tools for future exploration. IMPORTANCE Our study describes the first in vivo transposon sequencing (Tn-seq) analysis of B. pertussis and identifies genes predicted to be essential for in vivo growth in a murine model of intranasal infection, generating key resources for future investigations into B. pertussis pathogenesis and vaccine design
Intercalated theophylline-smectite hybrid for pH-mediated delivery
On the basis of their large specific surface areas, high adsorption and cation exchange capacities, swelling potential and low toxicity, natural smectite clays are attractive substrates for the gastric protection of neutral and cationic drugs. Theophylline is an amphoteric xanthine derivative that is widely used as a bronchodilator in the treatment of asthma and chronic obstructive pulmonary disease. This study considers the in vitro uptake and release characteristics of the binary theophylline-smectite system. The cationic form of theophylline was readily ion exchanged into smectite clay at pH 1.2 with a maximum uptake of 67±2 mg g−1. Characterisation of the drug-clay hybrid system by powder X-ray diffraction analysis, Fourier transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy confirmed that the theophylline had been exclusively intercalated into the clay system in an amorphous form. The drug remained bound within the clay under simulated gastric conditions at pH 1.2; and the prolonged release of approximately 40% of the drug was observed in simulated intestinal fluid at pH 6.8 and 7.4 within a 2-h timeframe. The incomplete reversibility of the intercalation process was attributed to chemisorption of the drug within the clay lattice. These findings indicate that smectite clay is a potentially suitable vehicle for the safe passage of theophylline into the duodenum. Protection from absorption in the stomach and subsequent prolonged release in the small intestine are advantageous in reducing fluctuations in serum concentration which may impact therapeutic effect and toxicit
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