1,713 research outputs found
A core genetic module : the Mixed Feedback Loop
The so-called Mixed Feedback Loop (MFL) is a small two-gene network where
protein A regulates the transcription of protein B and the two proteins form a
heterodimer. It has been found to be statistically over-represented in
statistical analyses of gene and protein interaction databases and to lie at
the core of several computer-generated genetic networks. Here, we propose and
mathematically study a model of the MFL and show that, by itself, it can serve
both as a bistable switch and as a clock (an oscillator) depending on kinetic
parameters. The MFL phase diagram as well as a detailed description of the
nonlinear oscillation regime are presented and some biological examples are
discussed. The results emphasize the role of protein interactions in the
function of genetic modules and the usefulness of modelling RNA dynamics
explicitly.Comment: To be published in Physical Review
A framework for branched storytelling and matchmaking in multiplayer games
Video games often either have good single player campaign modes or good multi-player campaign-less modes. This paper presents a framework aimed at the full game development pipeline, from designers to programmers, to aid in creating multiplayer campaigns by providing components that help singleplayer story modes to be used in multiplayer interaction settings. We also propose a custom matchmaking system capable of matching players so as to intertwine their individual stories. The proposed framework has been validated in a case study. A set of experimental results show that the framework is capable of producing valuable story crossings and proper matchmaking.info:eu-repo/semantics/acceptedVersio
Proteasome Lid Bridges Mitochondrial Stress with Cdc53/Cullin1 NEDDylation Status
Cycles of Cdc53/Cullin1 rubylation (a.k.a NEDDylation) protect ubiquitin-E3 SCF (Skp1-Cullin1-F-box protein) complexes from self-destruction and play an important role in mediating the ubiquitination of key protein substrates involved in cell cycle progression, development, and survival. Cul1 rubylation is balanced by the COP9 signalosome (CSN), a multi-subunit derubylase that shows 1:1 paralogy to the 26 S proteasome lid. The turnover of SCF substrates and their relevance to various diseases is well studied, yet, the extent by which environmental perturbations influence Cul1 rubylation/derubylation cycles per se is still unclear. In this study, we show that the level of cellular oxidation serves as a molecular switch, determining Cullin1 rubylation/derubylation ratio. We describe a mutant of the proteasome lid subunit, Rpn11 that exhibits accumulated levels of Cullin1-Rub1 conjugates, a characteristic phenotype of csn mutants. By dissecting between distinct phenotypes of rpn11 mutants, proteasome and mitochondria dysfunction, we were able to recognize the high reactive oxygen species (ROS) production during the transition of cells into mitochondrial respiration, as a checkpoint of Cullin1 rubylation in a reversible manner. Thus, the study adds the rubylation cascade to the list of cellular pathways regulated by redox homeostasis
Converting genetic network oscillations into somite spatial pattern
In most vertebrate species, the body axis is generated by the formation of
repeated transient structures called somites. This spatial periodicity in
somitogenesis has been related to the temporally sustained oscillations in
certain mRNAs and their associated gene products in the cells forming the
presomatic mesoderm. The mechanism underlying these oscillations have been
identified as due to the delays involved in the synthesis of mRNA and
translation into protein molecules [J. Lewis, Current Biol. {\bf 13}, 1398
(2003)]. In addition, in the zebrafish embryo intercellular Notch signalling
couples these oscillators and a longitudinal positional information signal in
the form of an Fgf8 gradient exists that could be used to transform these
coupled temporal oscillations into the observed spatial periodicity of somites.
Here we consider a simple model based on this known biology and study its
consequences for somitogenesis. Comparison is made with the known properties of
somite formation in the zebrafish embryo . We also study the effects of
localized Fgf8 perturbations on somite patterning.Comment: 7 pages, 7 figure
Dissection of the Carboxyl-Terminal Domain of the Proteasomal Subunit Rpn11 in Maintenance of Mitochondrial Structure and Function
We have previously demonstrated that the C-terminal part of Rpn11, a deubiquitinating enzyme in the lid of the proteasome, is essential for maintaining a correct cell cycle and normal mitochondrial morphology and function. The two roles are apparently unlinked as the mitochondrial role is mapped to the Carboxy-terminus, whereas the catalytic deubiquitinating activity is found within the N-terminal region. The mitochondrial defects are observed in rpn11-m1 (originally termed mpr1-1), a mutation that generates Rpn11 lacking the last 31 amino acids. No mitochondrial phenotypes are recorded for mutations in the MPN/JAMM motif. In the present study, we investigated the participation of the last 31 amino acids of the Rpn11 protein by analysis of intragenic revertants and site-specific mutants. We identified a putative -helix necessary for the maintenance of a correct cell cycle and determined that a very short region at the C-terminus of Rpn11 is essential for the maintenance of tubular mitochondrial morphology. Furthermore, we show that expression of the C-terminal part of Rpn11 is able to complement in trans all of the rpn11-m1 mitochondrial phenotypes. Finally, we investigate the mechanisms by which Rpn11 controls the mitochondrial shape and show that Rpn11 may regulate the mitochondrial fission and tubulation processes
(Il)Legitimisation of the role of the nation state: Understanding of and reactions to Internet censorship in Turkey
This study aims to explore Turkish citizen-consumers' understanding of and reactions to censorship of websites in Turkey by using in-depth interviews and online ethnography. In an environment where sites such as YouTube and others are increasingly being banned, the citizen-consumers' macro-level understanding is that such censorship is part of a wider ideological plan and their micro-level understanding is that their relationship with the wider global network is reduced, in the sense that they have trouble accessing full information on products, services and experiences. The study revealed that citizen-consumers engage in two types of resistance strategies against such domination by the state: using irony as passive resistance, and using the very same technology used by the state to resist its domination
Fission yeast 26S proteasome mutants are multi-drug resistant due to stabilization of the pap1 transcription factor
Here we report the result of a genetic screen for mutants resistant to the microtubule poison methyl benzimidazol-2-yl carbamate (MBC) that were also temperature sensitive for growth. In total the isolated mutants were distributed in ten complementation groups. Cloning experiments revealed that most of the mutants were in essential genes encoding various 26S proteasome subunits. We found that the proteasome mutants are multi-drug resistant due to stabilization of the stress-activated transcription factor Pap1. We show that the ubiquitylation and ultimately the degradation of Pap1 depend on the Rhp6/Ubc2 E2 ubiquitin conjugating enzyme and the Ubr1 E3 ubiquitin-protein ligase. Accordingly, mutants lacking Rhp6 or Ubr1 display drug-resistant phenotypes
Communicable Ulcerative Colitis Induced by T-bet Deficiency in the Innate Immune System
Inflammatory bowel disease (IBD) has been attributed to overexuberant host immunity or the emergence of harmful intestinal flora. The transcription factor T-bet orchestrates inflammatory genetic programs in both adaptive and innate immunity. We describe a profound and unexpected function for T-bet in influencing the behavior of host inflammatory activity and commensal bacteria. T-bet deficiency in the innate immune system results in spontaneous and communicable ulcerative colitis in the absence of adaptive immunity and increased susceptibility to colitis in immunologically intact hosts. T-bet controls the response of the mucosal immune system to commensal bacteria by regulating TNF-α production in colonic dendritic cells, critical for colonic epithelial barrier maintenance. Loss of T-bet influences bacterial populations to become colitogenic, and this colitis is communicable to genetically intact hosts. These findings reveal a novel function for T-bet as a peacekeeper of host-commensal relationships and provide new perspectives on the pathophysiology of IBD
Fusion versus Breakup: Observation of Large Fusion Suppression for ^9Be + ^{208}Pb
Complete fusion excitation functions for Be + Pb have been
measured to high precision at near barrier energies. The experimental fusion
barrier distribution extracted from these data allows reliable prediction of
the expected complete fusion cross-sections. However, the measured
cross-sections are only 68% of those predicted. The large cross-sections
observed for incomplete fusion products support the interpretation that this
suppression of fusion is caused by Be breaking up into charged fragments
before reaching the fusion barrier. Implications for the fusion of radioactive
nuclei are discussed.Comment: RevTex, 11 pages, 2 postscript figures, to appear in PR
Quasielastic 12C(e,e'p) Reaction at High Momentum Transfer
We measured the 12C(e,e'p) cross section as a function of missing energy in
parallel kinematics for (q,w) = (970 MeV/c, 330 MeV) and (990 MeV/c, 475 MeV).
At w=475 MeV, at the maximum of the quasielastic peak, there is a large
continuum (E_m > 50 MeV) cross section extending out to the deepest missing
energy measured, amounting to almost 50% of the measured cross section. The
ratio of data to DWIA calculation is 0.4 for both the p- and s-shells. At w=330
MeV, well below the maximum of the quasielastic peak, the continuum cross
section is much smaller and the ratio of data to DWIA calculation is 0.85 for
the p-shell and 1.0 for the s-shell. We infer that one or more mechanisms that
increase with transform some of the single-nucleon-knockout into
multinucleon knockout, decreasing the valence knockout cross section and
increasing the continuum cross section.Comment: 14 pages, 7 figures, Revtex (multicol, prc and aps styles), to appear
in Phys Rev
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