516 research outputs found
Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin
Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio
Network Theory Analysis of Antibody-Antigen Reactivity Data: The Immune Trees at Birth and Adulthood
Motivation: New antigen microarray technology enables parallel recording of antibody reactivities with hundreds of antigens. Such data affords system level analysis of the immune system’s organization using methods and approaches from network theory. Here we measured the reactivity of 290 antigens (for both the IgG and IgM isotypes) of 10 healthy mothers and their term newborns. We constructed antigen correlation networks (or immune networks) whose nodes are the antigens and the edges are the antigen-antigen reactivity correlations, and we also computed their corresponding minimum spanning trees (MST) – maximal information reduced sub-graphs. We quantify the network organization (topology) in terms of the network theory divergence rate measure and rank the antigen importance in the full antigen correlation networks by the eigen-value centrality measure. This analysis makes possible the characterization and comparison of the IgG and IgM immune networks at birth (newborns) and adulthood (mothers) in terms of topology and node importance. Results: Comparison of the immune network topology at birth and adulthood revealed partial conservation of the IgG immune network topology, and significant reorganization of the IgM immune networks. Inspection of the antigen importance revealed some dominant (in terms of high centrality) antigens in the IgG and IgM networks at birth, which retain their importance at adulthood
Injecting Domain Knowledge in Electronic Medical Records to Improve Hospitalization Prediction
International audienceElectronic medical records (EMR) contain key information about the different symptomatic episodes that a patient went through. They carry a great potential in order to improve the well-being of patients and therefore represent a very valuable input for artificial intelligence approaches. However, the explicit knowledge directly available through these records remains limited, the extracted features to be used by machine learning algorithms do not contain all the implicit knowledge of medical expert. In order to evaluate the impact of domain knowledge when processing EMRs, we augment the features extracted from EMRs with ontological resources before turning them into vectors used by machine learning algorithms. We evaluate these augmentations with several machine learning algorithms to predict hospitalization. Our approach was experimented on data from the PRIMEGE PACA database that contains more than 350,000 consultations carried out by 16 general practitioners (GPs)
Computational methodology to determine fluid related parameters on non regular three-dimensional scaffolds
The application of three-dimensional (3D) biomaterials
to facilitate the adhesion, proliferation, and differentiation
of cells has been widely studied for tissue engineering
purposes. The fabrication methods used to improve the
mechanical response of the scaffold produce complex and
non regular structures. Apart from the mechanical aspect, the
fluid behavior in the inner part of the scaffold should also be
considered. Parameters such as permeability (k) or wall shear
stress (WSS) are important aspects in the provision of
nutrients, the removal of metabolic waste products or the
mechanically-induced differentiation of cells attached in the
trabecular network of the scaffolds. Experimental measurements
of these parameters are not available in all labs.
However, fluid parameters should be known prior to other
types of experiments. The present work compares an
experimental study with a computational fluid dynamics
(CFD) methodology to determine the related fluid parameters
(k and WSS) of complex non regular poly(L-lactic acid)
scaffolds based only on the treatment of microphotographic
images obtained with a microCT (lCT). The CFD analysis
shows similar tendencies and results with low relative
difference compared to those of the experimental study, for
high flow rates. For low flow rates the accuracy of this
prediction reduces. The correlation between the computational
and experimental results validates the robustness of the
proposed methodology.The authors gratefully acknowledge research support from the Spanish Ministry of Science and Innovation through research project DPI2010-20399-C04-01. The Instituto de Salud Carlos III (ISCIII) through the CIBER initiative and the Platform for Biological Tissue Characterization of the Centro de Investigacion Biomedica en Red en Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN) are also gratefully acknowledged.Acosta Santamaría, VA.; Malvé, M.; Duizabo, A.; Mena Tobar, A.; Gallego Ferrer, G.; García Aznar, J.; Doblare Castellano, M.... (2013). Computational methodology to determine fluid related parameters on non regular three-dimensional scaffolds. Annals of Biomedical Engineering. 41(11):2367-2380. https://doi.org/10.1007/s10439-013-0849-8S236723804111Acosta Santamaría, V., H. Deplaine, D. Mariggió, A. R. Villanueva-Molines, J. M. García-Aznar, J. L. Gómez Ribelles, M. Doblaré, G. Gallego Ferrer, and I. Ochoa. 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Hsieh, T. Y. Hsien, L. T. Hou, J. Y. Lai, and D. M. Wang. Preparation of porous scaffolds by using freeze-extraction and freeze-gelation methods. Biomaterials 25(1):129–138, 2004.Hutmacher, D. W., J. T. Schantz, C. X. Lam, K. C. Tan, and T. C. Lim. State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective. J. Tissue Eng. Regen. Med. 1(4):245–260, 2007.Izal, I., P. Aranda, P. Sanz-Ramos, P. Ripalda, G. Mora, F. Granero-Moltó, H. Deplaine, J. L. Gómez-Ribelles, G. G. Ferrer, V. Acosta, I. Ochoa, J. M. García-Aznar, E. J. Andreu, M. Monleón-Pradas, M. Doblaré, and F. Prósper. Culture of human bone marrow-derived mesenchymal stem cells on of poly(l-lactic acid) scaffolds: potential application for the tissue engineering of cartilage. Knee Surg. Sports Traumatol. Arthrosc., 2012.Kapur, S., D. J. Baylink, and K. H. Lau. 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Flow modelling within a scaffold under the influence of uni-axial and bi-axial bioreactor rotation. J. Biotechnol. 119:181–196, 2005.Sjollema, J., and H. J. Busscher. Deposition of polystyrene latex-particles toward polymethylmethacrylate in a parallel plate flow cell. J. Colloid Interface Sci. 132(2):382–394, 1989.Truscello, S., G. Kerckhofs, S. Van Bael, G. Pyka, J. Schrooten, and H. Van Oosterwyck. Prediction of permeability of regular scaffolds for skeletal tissue engineering: a combined computational and experimental study. Acta Biomater. 8(4):1648–1658, 2012.Woodfield, T. B., J. Malda, J. Wijn, F. Péters, J. Riesle, and C. A. van Blitterswijk. Design of porous scaffolds for cartilage tissue engineering using a three-dimensional fiber-deposition technique. Biomaterials 25(18):4149–4161, 2004
Close 3D proximity of evolutionary breakpoints argues for the notion of spatial synteny
<p>Abstract</p> <p>Background</p> <p>Folding and intermingling of chromosomes has the potential of bringing close to each other loci that are very distant genomically or even on different chromosomes. On the other hand, genomic rearrangements also play a major role in the reorganisation of loci proximities. Whether the same loci are involved in both mechanisms has been studied in the case of somatic rearrangements, but never from an evolutionary standpoint.</p> <p>Results</p> <p>In this paper, we analysed the correlation between two datasets: (i) whole-genome chromatin contact data obtained in human cells using the Hi-C protocol; and (ii) a set of breakpoint regions resulting from evolutionary rearrangements which occurred since the split of the human and mouse lineages. Surprisingly, we found that two loci distant in the human genome but adjacent in the mouse genome are significantly more often observed in close proximity in the human nucleus than expected. Importantly, we show that this result holds for loci located on the same chromosome regardless of the genomic distance separating them, and the signal is stronger in gene-rich and open-chromatin regions.</p> <p>Conclusions</p> <p>These findings strongly suggest that part of the 3D organisation of chromosomes may be conserved across very large evolutionary distances. To characterise this phenomenon, we propose to use the notion of spatial synteny which generalises the notion of genomic synteny to the 3D case.</p
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
X-ray emission from the Sombrero galaxy: discrete sources
We present a study of discrete X-ray sources in and around the
bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival
Chandra observations with a total exposure of ~200 ks. With a detection limit
of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30
kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler
et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS
observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray
binaries (LMXBs). We quantify the differential luminosity functions (LFs) for
both the detected GC and field LMXBs, whose power-low indices (~1.1 for the
GC-LF and ~1.6 for field-LF) are consistent with previous studies for
elliptical galaxies. With precise sky positions of the GCs without a detected
X-ray source, we further quantify, through a fluctuation analysis, the GC LF at
fainter luminosities down to 1E35 erg/s. The derived index rules out a
faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent
findings in several elliptical galaxies and the bulge of M31. On the other
hand, the 2-6 keV unresolved emission places a tight constraint on the field
LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101
sources in the halo of Sombrero. The presence of these sources cannot be
interpreted as galactic LMXBs whose spatial distribution empirically follows
the starlight. Their number is also higher than the expected number of cosmic
AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray
surveys. We suggest that either the cosmic X-ray background is unusually high
in the direction of Sombrero, or a distinct population of X-ray sources is
present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres
Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV
The azimuthal anisotropy of charged particles in PbPb collisions at
nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS
detector at the LHC over an extended transverse momentum (pt) range up to
approximately 60 GeV. The data cover both the low-pt region associated with
hydrodynamic flow phenomena and the high-pt region where the anisotropies may
reflect the path-length dependence of parton energy loss in the created medium.
The anisotropy parameter (v2) of the particles is extracted by correlating
charged tracks with respect to the event-plane reconstructed by using the
energy deposited in forward-angle calorimeters. For the six bins of collision
centrality studied, spanning the range of 0-60% most-central events, the
observed v2 values are found to first increase with pt, reaching a maximum
around pt = 3 GeV, and then to gradually decrease to almost zero, with the
decline persisting up to at least pt = 40 GeV over the full centrality range
measured.Comment: Replaced with published version. Added journal reference and DO
Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy
A search for new physics is performed in events with two same-sign isolated
leptons, hadronic jets, and missing transverse energy in the final state. The
analysis is based on a data sample corresponding to an integrated luminosity of
4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of
7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of
140 increase in integrated luminosity over previously published results. The
observed yields agree with the standard model predictions and thus no evidence
for new physics is found. The observations are used to set upper limits on
possible new physics contributions and to constrain supersymmetric models. To
facilitate the interpretation of the data in a broader range of new physics
scenarios, information on the event selection, detector response, and
efficiencies is provided.Comment: Published in Physical Review Letter
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