65 research outputs found
Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire
We hypothesized that the scarcity of N-nucleotides might contribute to the inability of the neonate
to mount a robust allergic immune response. To test this, we used terminal deoxyribunucleotidyl
Transferase defcient (TdTâ/â) mice, which express âfetal-likeâ T cell receptor and immunoglobulin
repertoires with largely germline-encoded CDR3 regions. Intraperitoneal sensitization was followed
by aerosol provocation with either PBS or the allergen OVA in both TdTâ/â mice and wild-type mice
to develop allergic respiratory infammation. The efects of this procedure were investigated by lung
function test, immunological analysis of serum and brochoalveolar lavage. The local TH2 cytokine
milieu was signifcantly attenuated in TdTâ/â mice. Within this group, the induction of total IgE levels
was also signifcantly reduced after sensitization. TdTâ/â mice showed a tendency toward reduced
eosinophilic infow into the bronchial tubes, which was associated with the elimination of respiratory
hyperreactivity. In conclusion, in a murine model of allergic airway infammation, the expression
of fetal-like antigen receptors was associated with potent indications of a reduced ability to mount
an asthma phenotype. This underlines the importance of somatically-generated antigen-receptor
repertoire diversity in type one allergic immune responses and suggests that the fetus may be
protected from allergic responses, at least in part, by controlling N addition
Immunogenetic novelty confers a selective advantage in hostâpathogen coevolution
The major histocompatibility complex (MHC) is crucial to the adaptive immune response of vertebrates and is among the most polymorphic gene families known. Its high diversity is usually attributed to selection imposed by fast-evolving pathogens. Pathogens are thought to evolve to escape recognition by common immune alleles, and, hence, novel MHC alleles, introduced through mutation, recombination, or gene flow, are predicted to give hosts superior resistance. Although this theoretical prediction underpins hostâpathogen âRed Queenâ coevolution, it has not been demonstrated in the context of natural MHC diversity. Here, we experimentally tested whether novel MHC variants (both alleles and functional âsupertypesâ) increased resistance of guppies (Poecilia reticulata) to a common ectoparasite (Gyrodactylus turnbulli). We used exposure-controlled infection trials with wild-sourced parasites, and Gyrodactylus-naĂŻve host fish that were F2 descendants of crossed wild populations. Hosts carrying MHC variants (alleles or supertypes) that were new to a given parasite population experienced a 35â37% reduction in infection intensity, but the number of MHC variants carried by an individual, analogous to heterozygosity in single-locus systems, was not a significant predictor. Our results provide direct evidence of novel MHC variant advantage, confirming a fundamental mechanism underpinning the exceptional polymorphism of this gene family and highlighting the role of immunogenetic novelty in hostâpathogen coevolution
Tetramodal therapy with transurethral resection followed by chemoradiation in combination with hyperthermia for muscle-invasive bladder cancer: early results of a multicenter phase IIB study.
BACKGROUND
Transurethral resection of bladder tumor (TUR-BT) followed by chemoradiation (CRT) is a valid treatment option for patients with muscle-invasive bladder cancer (MIBC). This study aimed to investigate the efficacy of a tetramodal approach with additional regional hyperthermia (RHT).
METHODS
Patients with stages T2-4 MIBC were recruited at two institutions. Treatment consisted of TUR-BT followed by radiotherapy at doses of 57-58.2âGy with concurrent weekly platinum-based chemotherapy and weekly deep RHT (41-43â°C, 60âmin) within two hours of radiotherapy. The primary endpoint was a complete response six weeks after the end of treatment. Further endpoints were cystectomy-free rate, progression-free survival (PFS), local recurrence-free survival (LRFS), overall survival (OS) and toxicity. Quality of life (QoL) was assessed at follow-up using the EORTC-QLQ-C30 and QLQ-BM30 questionnaires. Due to slow accrual, an interim analysis was performed after the first stage of the two-stage design.
RESULTS
Altogether 27 patients were included in the first stage, of these 21 patients with a median age of 73âyears were assessable. The complete response rate of evaluable patients six weeks after therapy was 93%. The 2-year cystectomy-free rate, PFS, LRFS and OS rates were 95%, 76%, 81% and 86%, respectively. Tetramodal treatment was well tolerated with acute and late G3-4 toxicities of 10% and 13%, respectively, and a tendency to improve symptom-related quality of life (QoL) one year after therapy.
CONCLUSION
Tetramodal therapy of T2-T4 MIBC is promising with excellent local response, moderate toxicity and good QoL. This study deserves continuation into the second stage
Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory
The Auger Engineering Radio Array (AERA) is part of the Pierre Auger
Observatory and is used to detect the radio emission of cosmic-ray air showers.
These observations are compared to the data of the surface detector stations of
the Observatory, which provide well-calibrated information on the cosmic-ray
energies and arrival directions. The response of the radio stations in the 30
to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of
the incoming electric field. For the latter, the energy deposit per area is
determined from the radio pulses at each observer position and is interpolated
using a two-dimensional function that takes into account signal asymmetries due
to interference between the geomagnetic and charge-excess emission components.
The spatial integral over the signal distribution gives a direct measurement of
the energy transferred from the primary cosmic ray into radio emission in the
AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air
shower arriving perpendicularly to the geomagnetic field. This radiation energy
-- corrected for geometrical effects -- is used as a cosmic-ray energy
estimator. Performing an absolute energy calibration against the
surface-detector information, we observe that this radio-energy estimator
scales quadratically with the cosmic-ray energy as expected for coherent
emission. We find an energy resolution of the radio reconstruction of 22% for
the data set and 17% for a high-quality subset containing only events with at
least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO
Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy
We measure the energy emitted by extensive air showers in the form of radio
emission in the frequency range from 30 to 80 MHz. Exploiting the accurate
energy scale of the Pierre Auger Observatory, we obtain a radiation energy of
15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV
arriving perpendicularly to a geomagnetic field of 0.24 G, scaling
quadratically with the cosmic-ray energy. A comparison with predictions from
state-of-the-art first-principle calculations shows agreement with our
measurement. The radiation energy provides direct access to the calorimetric
energy in the electromagnetic cascade of extensive air showers. Comparison with
our result thus allows the direct calibration of any cosmic-ray radio detector
against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI.
Supplemental material in the ancillary file
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Post-mortem volatiles of vertebrate tissue
Volatile emission during vertebrate decay is a complex process that is understood incompletely. It depends on many factors. The main factor is the metabolism of the microbial species present inside and on the vertebrate. In this review, we combine the results from studies on volatile organic compounds (VOCs) detected during this decay process and those on the biochemical formation of VOCs in order to improve our understanding of the decay process. Micro-organisms are the main producers of VOCs, which are by- or end-products of microbial metabolism. Many microbes are already present inside and on a vertebrate, and these can initiate microbial decay. In addition, micro-organisms from the environment colonize the cadaver. The composition of microbial communities is complex, and communities of different species interact with each other in succession. In comparison to the complexity of the decay process, the resulting volatile pattern does show some consistency. Therefore, the possibility of an existence of a time-dependent core volatile pattern, which could be used for applications in areas such as forensics or food science, is discussed. Possible microbial interactions that might alter the process of decay are highlighted
The effect of the geomagnetic field on cosmic ray energy estimates and large scale anisotropy searches on data from the Pierre Auger Observatory
We present a comprehensive study of the influence of the geomagnetic field on
the energy estimation of extensive air showers with a zenith angle smaller than
, detected at the Pierre Auger Observatory. The geomagnetic field
induces an azimuthal modulation of the estimated energy of cosmic rays up to
the ~2% level at large zenith angles. We present a method to account for this
modulation of the reconstructed energy. We analyse the effect of the modulation
on large scale anisotropy searches in the arrival direction distributions of
cosmic rays. At a given energy, the geomagnetic effect is shown to induce a
pseudo-dipolar pattern at the percent level in the declination distribution
that needs to be accounted for.Comment: 20 pages, 14 figure
The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases
The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article
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