9,793 research outputs found
Identifying dynamical modules from genetic regulatory systems: applications to the segment polarity network
BACKGROUND
It is widely accepted that genetic regulatory systems are 'modular', in that the whole system is made up of smaller 'subsystems' corresponding to specific biological functions. Most attempts to identify modules in genetic regulatory systems have relied on the topology of the underlying network. However, it is the temporal activity (dynamics) of genes and proteins that corresponds to biological functions, and hence it is dynamics that we focus on here for identifying subsystems.
RESULTS
Using Boolean network models as an exemplar, we present a new technique to identify subsystems, based on their dynamical properties. The main part of the method depends only on the stable dynamics (attractors) of the system, thus requiring no prior knowledge of the underlying network. However, knowledge of the logical relationships between the network components can be used to describe how each subsystem is regulated. To demonstrate its applicability to genetic regulatory systems, we apply the method to a model of the Drosophila segment polarity network, providing a detailed breakdown of the system.
CONCLUSION
We have designed a technique for decomposing any set of discrete-state, discrete-time attractors into subsystems. Having a suitable mathematical model also allows us to describe how each subsystem is regulated and how robust each subsystem is against perturbations. However, since the subsystems are found directly from the attractors, a mathematical model or underlying network topology is not necessarily required to identify them, potentially allowing the method to be applied directly to experimental expression data
Identification of a Conserved Anti-Apoptotic Protein That Modulates the Mitochondrial Apoptosis Pathway
Here we identified an evolutionarily highly conserved and ubiquitously expressed protein (C9orf82) that shows structural similarities to the death effector domain of apoptosis-related proteins. RNAi knockdown of C9orf82 induced apoptosis in A-549 and MCF7/casp3-10b lung and breast carcinoma cells, respectively, but not in cells lacking caspase-3, caspase-10 or both. Apoptosis was associated with activated caspases-3, -8, -9 and -10, and inactivation of caspases 10 or 3 was sufficient to block apoptosis in this pathway. Apoptosis upon knockdown of C9orf82 was associated with increased caspase-10 expression and activation, which was required for the generation of an 11 kDa tBid fragment and activation of Caspase-9. These data suggest that C9orf82 functions as an anti-apoptotic protein that modulates a caspase-10 dependent mitochondrial caspase-3/9 feedback amplification loop. We designate this ubiquitously expressed and evolutionarily conserved anti-apoptotic protein Conserved Anti-Apoptotic Protein (CAAP). We also demonstrated that treatment of MCF7/casp3-10b cells with staurosporine and etoposides induced apoptosis and knockdown of CAAP expression. This implies that the CAAP protein could be a target for chemotherapeutic agents
Photodetachment study of the 1s3s4s ^4S resonance in He^-
A Feshbach resonance associated with the 1s3s4s ^{4}S state of He^{-} has
been observed in the He(1s2s ^{3}S) + e^- (\epsilon s) partial photodetachment
cross section. The residual He(1s2s ^{3}S) atoms were resonantly ionized and
the resulting He^+ ions were detected in the presence of a small background. A
collinear laser-ion beam apparatus was used to attain both high resolution and
sensitivity. We measured a resonance energy E_r = 2.959 255(7) eV and a width
\Gamma = 0.19(3) meV, in agreement with a recent calculation.Comment: LaTeX article, 4 pages, 3 figures, 21 reference
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On the re-acceleration of bunched beams
We examine the re-acceleration of a bunched beam through a linear induction accelerator (LIA) cavity, with attention to the energy lost through coupling to the TM modes of the structure. We find that the energy lost at 1 kA peak current is a small fraction of the boost which the LIA is designed to impart. We discuss implications for a Relativistic Klystron or Free Electron Laser (FEL) version of the Two-Beam Accelerator (TBA). 18 refs., 5 figs., 1 tab
A genetically modified adenoviral vector with a phage display-derived peptide incorporated into fiber fibritin chimera prolongs survival in experimental glioma
The dismal clinical context of advanced-grade glioma demands the development of novel therapeutic strategies with direct patient impact. Adenovirus-mediated virotherapy represents a potentially effective approach for glioma therapy. In this research, we generated a novel glioma-specific adenovirus by instituting more advanced genetic modifications that can maximize the efficiency and safety of therapeutic adenoviral vectors. In this regard, a glioma-specific targeted fiber was developed through the incorporation of previously published glioma-specific, phage-panned peptide (VWT peptide) on a fiber fibritin-based chimeric fiber, designated as âGliomaFF.â We showed that the entry of this virus was highly restricted to glioma cells, supporting the specificity imparted by the phage-panned peptide. In addition, the stability of the targeting moiety presented by fiber fibritin structure permitted greatly enhanced infectivity. Furthermore, the replication of this virus was restricted in glioma cells by controlling expression of the E1 gene under the activity of the tumor-specific survivin promoter. Using this approach, we were able to explore the combinatorial efficacy of various adenoviral modifications that could amplify the specificity, infectivity, and exclusive replication of this therapeutic adenovirus in glioma. Finally, virotherapy with this modified virus resulted in up to 70% extended survival in an in vivo murine glioma model. These data demonstrate that this novel adenoviral vector is a safe and efficient treatment for this difficult malignancy
Deterministic and stochastic descriptions of gene expression dynamics
A key goal of systems biology is the predictive mathematical description of
gene regulatory circuits. Different approaches are used such as deterministic
and stochastic models, models that describe cell growth and division explicitly
or implicitly etc. Here we consider simple systems of unregulated
(constitutive) gene expression and compare different mathematical descriptions
systematically to obtain insight into the errors that are introduced by various
common approximations such as describing cell growth and division by an
effective protein degradation term. In particular, we show that the population
average of protein content of a cell exhibits a subtle dependence on the
dynamics of growth and division, the specific model for volume growth and the
age structure of the population. Nevertheless, the error made by models with
implicit cell growth and division is quite small. Furthermore, we compare
various models that are partially stochastic to investigate the impact of
different sources of (intrinsic) noise. This comparison indicates that
different sources of noise (protein synthesis, partitioning in cell division)
contribute comparable amounts of noise if protein synthesis is not or only
weakly bursty. If protein synthesis is very bursty, the burstiness is the
dominant noise source, independent of other details of the model. Finally, we
discuss two sources of extrinsic noise: cell-to-cell variations in protein
content due to cells being at different stages in the division cycles, which we
show to be small (for the protein concentration and, surprisingly, also for the
protein copy number per cell) and fluctuations in the growth rate, which can
have a significant impact.Comment: 23 pages, 5 figures; Journal of Statistical physics (2012
The astrometric Gaia-FUN-SSO observation campaign of 99 942 Apophis
Astrometric observations performed by the Gaia Follow-Up Network for Solar
System Objects (Gaia-FUN-SSO) play a key role in ensuring that moving objects
first detected by ESA's Gaia mission remain recoverable after their discovery.
An observation campaign on the potentially hazardous asteroid (99 942) Apophis
was conducted during the asteroid's latest period of visibility, from
12/21/2012 to 5/2/2013, to test the coordination and evaluate the overall
performance of the Gaia-FUN-SSO . The 2732 high quality astrometric
observations acquired during the Gaia-FUN-SSO campaign were reduced with the
Platform for Reduction of Astronomical Images Automatically (PRAIA), using the
USNO CCD Astrograph Catalogue 4 (UCAC4) as a reference. The astrometric
reduction process and the precision of the newly obtained measurements are
discussed. We compare the residuals of astrometric observations that we
obtained using this reduction process to data sets that were individually
reduced by observers and accepted by the Minor Planet Center. We obtained 2103
previously unpublished astrometric positions and provide these to the
scientific community. Using these data we show that our reduction of this
astrometric campaign with a reliable stellar catalog substantially improves the
quality of the astrometric results. We present evidence that the new data will
help to reduce the orbit uncertainty of Apophis during its close approach in
2029. We show that uncertainties due to geolocations of observing stations, as
well as rounding of astrometric data can introduce an unnecessary degradation
in the quality of the resulting astrometric positions. Finally, we discuss the
impact of our campaign reduction on the recovery process of newly discovered
asteroids.Comment: Accepted for publication in A&
The `Friction' of Vacuum, and other Fluctuation-Induced Forces
The static Casimir effect describes an attractive force between two
conducting plates, due to quantum fluctuations of the electromagnetic (EM)
field in the intervening space. {\it Thermal fluctuations} of correlated fluids
(such as critical mixtures, super-fluids, liquid crystals, or electrolytes) are
also modified by the boundaries, resulting in finite-size corrections at
criticality, and additional forces that effect wetting and layering phenomena.
Modified fluctuations of the EM field can also account for the `van der Waals'
interaction between conducting spheres, and have analogs in the
fluctuation--induced interactions between inclusions on a membrane. We employ a
path integral formalism to study these phenomena for boundaries of arbitrary
shape. This allows us to examine the many unexpected phenomena of the dynamic
Casimir effect due to moving boundaries. With the inclusion of quantum
fluctuations, the EM vacuum behaves essentially as a complex fluid, and
modifies the motion of objects through it. In particular, from the mechanical
response function of the EM vacuum, we extract a plethora of interesting
results, the most notable being: (i) The effective mass of a plate depends on
its shape, and becomes anisotropic. (ii) There is dissipation and damping of
the motion, again dependent upon shape and direction of motion, due to emission
of photons. (iii) There is a continuous spectrum of resonant cavity modes that
can be excited by the motion of the (neutral) boundaries.Comment: RevTex, 2 ps figures included. The presentation is completely
revised, and new sections are adde
Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens.
BackgroundTo determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed.MethodsTen CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system.ResultsAn average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR qâ<â0.05, fold change >2) were identified. Expression of selected DEGs (nâ=â32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90 % of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value <0.05, minimum inclusion level difference >0.1).ConclusionThe RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis
Quark-Gluon Matter
A concise review of the experimental and phenomenological progress in
high-energy heavy-ion physics over the past few years is presented. Emphasis is
put on measurements at BNL-RHIC and CERN-SPS which provide information on
fundamental properties of QCD matter at extreme values of temperature, density
and low-x. The new opportunities accessible at the LHC, which may help clarify
some of the current open issues, are also outlined.Comment: Minor changes to text. New refs. included. Updated figures with final
dat
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