Whole-exome and HLA sequencing in Febrile infection-related epilepsy syndrome

Febrile infection‐related epilepsy syndrome (FIRES) is a devastating epilepsy characterized by new‐onset refractory status epilepticus with a prior febrile infection. We performed exome sequencing in 50 individuals with FIRES, including 27 patient–parent trios and 23 single probands, none of whom had pathogenic variants in established genes for epilepsies or neurodevelopmental disorders. We also performed HLA sequencing in 29 individuals with FIRES and 529 controls, which failed to identify prominent HLA alleles. The genetic architecture of FIRES is substantially different from other developmental and epileptic encephalopathies, and the underlying etiology remains elusive, requiring novel approaches to identify the underlying causative factors

Nature of the Earth's earliest crust from hafnium isotopes in single detrital zircons

Continental crust forms from, and thus chemically depletes, the Earth's mantle. Evidence that the Earth's mantle was already chemically depleted by melting before the formation of today's oldest surviving crust has been presented in the form of Sm-Nd isotope studies of 3.8-4.0 billion years old rocks from Greenland(1-5) and Canada(5-7). But this interpretation has been questioned because of the possibility that subsequent perturbations may have re-equilibrated the neodymium-isotope compositions of these rocks(8). Independent and more robust evidence for the origin of the earliest crust and depletion of the Archaean mantle can potentially be provided by hafnium-isotope compositions of zircon, a mineral whose age can be precisely determined by U-Pb dating, and which can survive metamorphisms(4). But the amounts of hafnium in single zircon grains are too small for the isotopic composition to be precisely analysed by conventional methods. Here we report hafnium-isotope data, obtained using the new technique of multiple-collector plasma-source mass spectrometry(9), for 37 individual grains of the oldest known terrestrial zircons (from the Narryer Gneiss Complex, Australia, with U-Pb ages of up to 4.14 Gyr (refs 10-13)). We find that none of the grains has a depleted mantle signature, but that many were derived from a source with a hafnium-isotope composition similar to that of chondritic meteorites. Furthermore, more than half of the analysed grains seem to have formed by remelting of significantly older crust, indicating that crustal preservation and subsequent reworking might have been important processes from earliest times.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62681/1/399252a0.pd

How and when plume zonation appeared during the 132 Myr evolution of the Tristan Hotspot

Increasingly, spatial geochemical zonation, present as geographically distinct, subparallel trends, is observed along hotspot tracks, such as Hawaii and the Galapagos. The origin of this zonation is currently unclear. Recently zonation was found along the last B70 Myr of the Tristan-Gough hotspot track. Here we present new Sr–Nd–Pb–Hf isotope data from the older parts of this hotspot track (Walvis Ridge and Rio Grande Rise) and re-evaluate published data from the Etendeka and Parana flood basalts erupted at the initiation of the hotspot track. We show that only the enriched Gough, but not the less-enriched Tristan, component is present in the earlier (70–132 Ma) history of the hotspot. Here we present a model that can explain the temporal evolution and origin of plume zonation for both the Tristan-Gough and Hawaiian hotspots, two end member types of zoned plumes, through processes taking place in the plume sources at the base of the lower mantle

Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management

Background. During the chronic stage of Complex Regional Pain Syndrome (CRPS), impaired microcirculation is related to increased vasoconstriction, tissue hypoxia, and metabolic tissue acidosis in the affected limb. Several mechanisms may be responsible for the ischemia and pain in chronic cold CPRS. Discussion. The diminished blood flow may be caused by either sympathetic dysfunction, hypersensitivity to circulating catecholamines, or endothelial dysfunction. The pain may be of neuropathic, inflammatory, nociceptive, or functional nature, or of mixed origin. Summary. The origin of the pain should be the basis of the symptomatic therapy. Since the difference in temperature between both hands fluctuates over time in cold CRPS, when in doubt, the clinician should prioritize the patient's report of a persistent cold extremity over clinical tests that show no difference. Future research should focus on developing easily applied methods for clinical use to differentiate between central and peripheral blood flow regulation disorders in individual patients