6 research outputs found
Brief Report: Association of Tumor Necrosis Factor Receptor–Associated Periodic Syndrome With Gonosomal Mosaicism of a Novel 24-Nucleotide TNFRSF1A Deletion
Objective: To investigate the molecular cause of persistent fevers in a patient returning from working overseas, in whom investigations for tropical diseases yielded negative results. / Methods: DNA was extracted from the patient's whole blood, leukocyte subpopulations, saliva, hair root, and sperm. The TNFRSF1A gene was analyzed by polymerase chain reaction (PCR), allele-specific PCR, Sanger sequencing, and next-generation sequencing. In silico molecular modeling was performed to predict the structural and functional consequences of the tumor necrosis factor receptor (TNFR) type I protein mutation in the extracellular domain. / Results: Sanger sequencing corroborated by allele-specific PCR detected a novel in-frame deletion of 24 nucleotides (c.255_278del) in the TNFRSF1A gene, and this was subsequently confirmed using next-generation sequencing methods (targeted sequencing and amplicon-based deep sequencing). Results of amplicon-based deep sequencing revealed variable frequency of the mutant allele among different cell lines, including sperm, thus supporting the presence of gonosomal TNFRSF1A mosaicism. The patient had a complete response to treatment with interleukin-1 (IL-1) blockade, with resolution of symptoms and normalization of acute-phase protein levels. / Conclusion: We describe the first case of gonosomal TNFRSF1A mosaicism in a patient with TNFR-associated periodic syndrome (TRAPS), which was attributable to a novel, somatic 24-nucleotide in-frame deletion. The clinical picture in this patient, including the complete response to IL-1 blockade, was typical of that found in TRAPS. This case adds TRAPS to the list of dominantly inherited autoinflammatory diseases reported to be caused by somatic (or postzygotic) mutation
Deletion of Metabotropic Glutamate Receptors 2 and 3 (mGlu2 & mGlu3) in Mice Disrupts Sleep and Wheel-Running Activity, and Increases the Sensitivity of the Circadian System to Light
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The LHCb Upgrade I
Abstract
The LHCb upgrade represents a major change of the
experiment. The detectors have been almost completely renewed to
allow running at an instantaneous luminosity five times larger than
that of the previous running periods. Readout of all detectors into
an all-software trigger is central to the new design, facilitating
the reconstruction of events at the maximum LHC interaction rate,
and their selection in real time. The experiment's tracking system
has been completely upgraded with a new pixel vertex detector, a
silicon tracker upstream of the dipole magnet and three
scintillating fibre tracking stations downstream of the magnet. The
whole photon detection system of the RICH detectors has been renewed
and the readout electronics of the calorimeter and muon systems have
been fully overhauled. The first stage of the all-software trigger
is implemented on a GPU farm. The output of the trigger provides a
combination of totally reconstructed physics objects, such as tracks
and vertices, ready for final analysis, and of entire events which
need further offline reprocessing. This scheme required a complete
revision of the computing model and rewriting of the experiment's
software.</jats:p