7,350 research outputs found
Detection of Marker Associated with CTC in Colorectal Cancer in Mononuclear Cells of Patients with Benign Inflammatory Intestinal Diseases
Colorectal carcinoma (CRC) belongs to the most common tumor entities in western countries. Circulating tumor cells (CTC) in blood of CRC patients are a powerful prognostic and predictive biomarker. However, whether CTC-associated markers can also be used for early CRC detection and discrimination from benign diseases is not known. This study investigated the presence of CTC-associated markers CK20, PLS3, LAD1, and DEFA5 in blood of patients with benign inflammatory intestinal disease (IID) and their correlation with malignancy. The detection rate of CK20 and DEFA5 significantly differed between diseased patients and healthy controls. LAD1 and PLS3 were detected in all samples with clear differences in gene expression. DEFA5 expression was higher in CRC and IID patients compared to healthy donors, while CK20 and PLS3 were lower in CRC compared to IID patients or healthy controls. Overall, all CTC-associated markers were detectable in blood of IID patients, but not correlating with inflammation severity. Finally, PLS3 emerged as a suitable marker for differentiation between malignant and non-malignant intestinal diseases or healthy controls, however its suitability for early CRC detection needs to be further validated
Characterisation of cultivation of the human cell line AGE1.HN.AAT
Skerhutt EM, Scholz S, Niklas J, et al. Characterisation of cultivation of the human cell line AGE1.HN.AAT. BMC Proceedings. 2011;5(8)
Phylogenetic and Molecular Analysis of Food-Borne Shiga Toxin-Producing Escherichia coli
Seventy-five food-associated Shiga toxin-producing Escherichia coli (STEC)
strains were analyzed by molecular and phylogenetic methods to describe their
pathogenic potential. The presence of the locus of proteolysis activity (LPA),
the chromosomal pathogenicity island (PAI) PAI ICL3, and the autotransporter-
encoding gene sabA was examined by PCR. Furthermore, the occupation of the
chromosomal integration sites of the locus of enterocyte effacement (LEE),
selC, pheU, and pheV, as well as the Stx phage integration sites yehV, yecE,
wrbA, z2577, and ssrA, was analyzed. Moreover, the antibiotic resistance
phenotypes of all STEC strains were determined. Multilocus sequence typing
(MLST) was performed, and sequence types (STs) and sequence type complexes
(STCs) were compared with those of 42 hemolytic-uremic syndrome
(HUS)-associated enterohemorrhagic E. coli (HUSEC) strains. Besides 59 STs and
4 STCs, three larger clusters were defined in this strain collection. Clusters
A and C consist mostly of highly pathogenic eae-positive HUSEC strains and
some related food-borne STEC strains. A member of a new O26 HUS-associated
clone and the 2011 outbreak strain E. coli O104:H4 were found in cluster A.
Cluster B comprises only eae-negative food-borne STEC strains as well as
mainly eae-negative HUSEC strains. Although food-borne strains of cluster B
were not clearly associated with disease, serotypes of important pathogens,
such as O91:H21 and O113:H21, were in this cluster and closely related to the
food-borne strains. Clonal analysis demonstrated eight closely related genetic
groups of food-borne STEC and HUSEC strains that shared the same ST and were
similar in their virulence gene composition. These groups should be considered
with respect to their potential for human infection
Application to the Analysis of Germinal Center Reactions In Vivo
Simultaneous detection of multiple cellular and molecular players in their
native environment, one of the keys to a full understanding of immune
processes, remains challenging for in vivo microscopy. Here, we present a
synergistic strategy for spectrally multiplexed in vivo imaging composed of
(i) triple two-photon excitation using spatiotemporal synchronization of two
femtosecond lasers, (ii) a broad set of fluorophores with emission ranging
from blue to near infrared, (iii) an effective spectral unmixing algorithm.
Using our approach, we simultaneously excite and detect seven fluorophores
expressed in distinct cellular and tissue compartments, plus second harmonics
generation from collagen fibers in lymph nodes. This enables us to visualize
the dynamic interplay of all the central cellular players during germinal
center reactions. While current in vivo imaging typically enables recording
the dynamics of 4 tissue components at a time, our strategy allows a more
comprehensive analysis of cellular dynamics involving 8 single-labeled
compartments. It enables to investigate the orchestration of multiple cellular
subsets determining tissue function, thus, opening the way for a mechanistic
understanding of complex pathophysiologic processes in vivo. In the future,
the design of transgenic mice combining a larger spectrum of fluorescent
proteins will reveal the full potential of our method
The potential for histone deacetylase (HDAC) inhibitors as cestocidal drugs
Background: Echinococcosis and cysticercosis are neglected tropical diseases caused by cestode parasites (family Taeniidae). Not only there is a small number of approved anthelmintics for the treatment of these cestodiases, but also some of them are not highly effective against larval stages, such that identifying novel drug targets and their associated compounds is critical. Histone deacetylase (HDAC) enzymes are validated drug targets in cancers and other diseases, and have been gaining relevance for developing new potential anti-parasitic treatments in the last years. Here, we present the anthelmintic profile for a panel of recently developed HDAC inhibitors against the model cestode Mesocestoides vogae (syn. M. corti).Methodology/principal findings: Phenotypic screening was performed on M. vogae by motility measurements and optical microscopic observations. Some HDAC inhibitors showed potent anthelmintic activities; three of them-entinostat, TH65, and TH92 -had pronounced anthelmintic effects, reducing parasite viability by ~100% at concentrations of ⤠20 ÎźM. These compounds were selected for further characterization and showed anthelmintic effects in the micromolar range and in a time- and dose-dependent manner. Moreover, these compounds induced major alterations on the morphology and ultrastructural features of M. vogae. The potencies of these compounds were higher than albendazole and the anthelmintic effects were irreversible. Additionally, we evaluated pairwise drug combinations of these HDAC inhibitors and albendazole. The results suggested a positive interaction in the anthelmintic effect for individual pairs of compounds. Due to the maximum dose approved for entinostat, adjustments in the dose regime and/or combinations with currently-used anthelmintic drugs are needed, and the selectivity of TH65 and TH92 towards parasite targets should be assessed.Conclusion, significance: The results presented here suggest that HDAC inhibitors represent novel and potent drug candidates against cestodes and pave the way to understanding the roles of HDACs in these parasites.Fil: Vaca, Hugo Rolando. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂŠdica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂŠdica; Argentina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en ProducciĂłn, Sanidad y Ambiente - Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Centro CientĂfico TecnolĂłgico Conicet - Mar del Plata. Instituto de Investigaciones en ProducciĂłn, Sanidad y Ambiente; ArgentinaFil: Celentano, Ana M.. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂŠdica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂŠdica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de MicrobiologĂa; ArgentinaFil: Toscanini, MarĂa Agustina. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂŠdica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂŠdica; ArgentinaFil: Heimburg, Tino. No especifĂca;Fil: Ghazy, Ehab. No especifĂca;Fil: Zeyen, Patrik. No especifĂca;Fil: Hauser, Alexander Thomas. Albert Ludwigs University of Freiburg; AlemaniaFil: Oliveira, Guilherme. Instituto TecnolĂłgico Vale.; BrasilFil: Elissondo, MarĂa Celina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en ProducciĂłn, Sanidad y Ambiente - Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Centro CientĂfico TecnolĂłgico Conicet - Mar del Plata. Instituto de Investigaciones en ProducciĂłn, Sanidad y Ambiente; ArgentinaFil: Jung, Manfred. Albert Ludwigs University of Freiburg; AlemaniaFil: Sippl, Wolfgang. No especifĂca;Fil: Camicia, Federico. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂŠdica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂŠdica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones CientĂficas y TĂŠcnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂŠdica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en MicrobiologĂa y ParasitologĂa MĂŠdica; Argentin
Extending PLE models into the mid-IR, far-IR & sub-mm
Simple pure luminosity evolution (PLE) models, in which galaxies brighten at
high redshift due to increased star-formation rates (SFRs), are known to
provide a good fit to the colours and number counts of galaxies throughout the
optical and near-infrared. We show that optically defined PLE models, where
dust reradiates absorbed optical light into infrared spectra composed of local
galaxy templates, fit galaxy counts and colours out to 8um and to at least
z=2.5. At 24-70um, the model is able to reproduce the observed source counts
with reasonable success if 16% of spiral galaxies show an excess in mid-IR flux
due to a warmer dust component and a higher SFR, in line with observations of
local starburst galaxies. There remains an under-prediction of the number of
faint-flux, high-z sources at 24um, so we explore how the evolution may be
altered to correct this. At 160um and longer wavelengths, the model fails, with
our model of normal galaxies accounting for only a few percent of sources in
these bands. However, we show that a PLE model of obscured AGN, which we have
previously shown to give a good fit to observations at 850um, also provides a
reasonable fit to the Herschel/BLAST number counts and redshift distributions
at 250-500um. In the context of a LCDM cosmology, an AGN contribution at
250-870um would remove the need to invoke a top-heavy IMF for high-redshift
starburst galaxies, although the excellent fit of the galaxy PLE model at
shorter wavelengths would still need to be explained.Comment: 14 pages, 11 figures; submitted to MNRA
A New Era in Extragalactic Background Light Measurements: The Cosmic History of Accretion, Nucleosynthesis and Reionization
(Brief Summary) What is the total radiative content of the Universe since the
epoch of recombination? The extragalactic background light (EBL) spectrum
captures the redshifted energy released from the first stellar objects,
protogalaxies, and galaxies throughout cosmic history. Yet, we have not
determined the brightness of the extragalactic sky from UV/optical to
far-infrared wavelengths with sufficient accuracy to establish the radiative
content of the Universe to better than an order of magnitude. Among many
science topics, an accurate measurement of the EBL spectrum from optical to
far-IR wavelengths, will address: What is the total energy released by stellar
nucleosynthesis over cosmic history? Was significant energy released by
non-stellar processes? Is there a diffuse component to the EBL anywhere from
optical to sub-millimeter? When did first stars appear and how luminous was the
reionization epoch? Absolute optical to mid-IR EBL spectrum to an
astrophysically interesting accuracy can be established by wide field imagingat
a distance of 5 AU or above the ecliptic plane where the zodiacal foreground is
reduced by more than two orders of magnitude.Comment: 7 pages; Science White Paper for the US Astro 2010-2020 Decadal
Survey. If interested in further community-wide efforts on this topic please
contact the first autho
A novel unconventional T cell population enriched in Crohn's disease
Objective One of the current hypotheses to explain the proinflammatory immune response in IBD is a dysregulated T cell reaction to yet unknown intestinal antigens. As such, it may be possible to identify disease-associated T cell clonotypes by analysing the peripheral and intestinal T-cell receptor (TCR) repertoire of patients with IBD and controls. Design We performed bulk TCR repertoire profiling of both the TCR alpha and beta chains using high-throughput sequencing in peripheral blood samples of a total of 244 patients with IBD and healthy controls as well as from matched blood and intestinal tissue of 59 patients with IBD and disease controls. We further characterised specific T cell clonotypes via single-cell RNAseq. Results We identified a group of clonotypes, characterised by semi-invariant TCR alpha chains, to be significantly enriched in the blood of patients with Crohn's disease (CD) and particularly expanded in the CD8+ T cell population. Single-cell RNAseq data showed an innate-like phenotype of these cells, with a comparable gene expression to unconventional T cells such as mucosal associated invariant T and natural killer T (NKT) cells, but with distinct TCRs. Conclusions We identified and characterised a subpopulation of unconventional Crohn-associated invariant T (CAIT) cells. Multiple evidence suggests these cells to be part of the NKT type II population. The potential implications of this population for CD or a subset thereof remain to be elucidated, and the immunophenotype and antigen reactivity of CAIT cells need further investigations in future studies
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis
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
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