Casein kinase iδ mutations in familial migraine and advanced sleep phase.

Migraine is a common disabling disorder with a significant genetic component, characterized by severe headache and often accompanied by nausea, vomiting, and light sensitivity. We identified two families, each with a distinct missense mutation in the gene encoding casein kinase Iδ (CKIδ), in which the mutation cosegregated with both the presence of migraine and advanced sleep phase. The resulting alterations (T44A and H46R) occurred in the conserved catalytic domain of CKIδ, where they caused reduced enzyme activity. Mice engineered to carry the CKIδ-T44A allele were more sensitive to pain after treatment with the migraine trigger nitroglycerin. CKIδ-T44A mice also exhibited a reduced threshold for cortical spreading depression (believed to be the physiological analog of migraine aura) and greater arterial dilation during cortical spreading depression. Astrocytes from CKIδ-T44A mice showed increased spontaneous and evoked calcium signaling. These genetic, cellular, physiological, and behavioral analyses suggest that decreases in CKIδ activity can contribute to the pathogenesis of migraine

Subseasonal-to-interdecadal variability of the Australian monsoon over North Queensland

Daily rainfall occurrence and amount at 11 stations over North Queensland are examined for summers 1958–1998, using a Hidden Markov Model (HMM). Daily rainfall variability is described in terms of the occurrence of five discrete ‘weather states’, identified by the HMM. Three states are characterized respectively by very wet, moderately wet, and dry conditions at most stations; two states have enhanced rainfall along the coast and dry conditions inland. Each HMM rainfall state is associated with a distinct atmospheric circulation regime. The two wet states are accompanied by monsoonal circulation patterns with large-scale ascent, low-level inflow from the north-west, and a phase reversal with height; the dry state is characterized by circulation anomalies of the opposite sense. Two of the states show significant associations with midlatitude synoptic waves. Variability of the monsoon on time-scales from subseasonal to interdecadal is interpreted in terms of changes in the frequency of occurrence of the five HMM rainfall states. Large subseasonal variability is identified in terms of active and break phases, and a highly variable monsoon onset date. The occurrence of the very wet and dry states is somewhat modulated by the Madden–Julian oscillation. On interannual time-scales, there are clear relationships with the El Niño–Southern Oscillation and Indian Ocean sea surface temperatures (SSTs). Interdecadal monsoonal variability is characterized by stronger monsoons during the 1970s, and weaker monsoons plus an increased prevalence of drier states in the later part of the record. Stochastic simulations of daily rainfall occurrence and amount at the 11 stations are generated by introducing predictors based on large-scale precipitation from (a) reanalysis data, (b) an atmospheric general circulation model (GCM) run with observed SST forcing and (c) antecedent June–August Pacific SST anomalies. The reanalysis large-scale precipitation yields relatively accurate station-level simulations of the interannual variability of daily rainfall amount and occurrence, with rainfall intensity less well simulated. At some stations, interannual variations in 10-day dry-spell frequency are also simulated reasonably well. The interannual quality of the simulations is markedly degraded when the GCM simulations are used as inputs, while antecedent Pacific SST inputs yield an anomaly correlation skill comparable to that of the GCM

Subseasonal-to-interdecadal variability of the Australian monsoon over North Queensland

Daily rainfall occurrence and amount at 11 stations over North Queensland are examined for summers 1958–1998, using a Hidden Markov Model (HMM). Daily rainfall variability is described in terms of the occurrence of five discrete ‘weather states’, identified by the HMM. Three states are characterized respectively by very wet, moderately wet, and dry conditions at most stations; two states have enhanced rainfall along the coast and dry conditions inland. Each HMM rainfall state is associated with a distinct atmospheric circulation regime. The two wet states are accompanied by monsoonal circulation patterns with large-scale ascent, low-level inflow from the north-west, and a phase reversal with height; the dry state is characterized by circulation anomalies of the opposite sense. Two of the states show significant associations with midlatitude synoptic waves. Variability of the monsoon on time-scales from subseasonal to interdecadal is interpreted in terms of changes in the frequency of occurrence of the five HMM rainfall states. Large subseasonal variability is identified in terms of active and break phases, and a highly variable monsoon onset date. The occurrence of the very wet and dry states is somewhat modulated by the Madden–Julian oscillation. On interannual time-scales, there are clear relationships with the El Niño–Southern Oscillation and Indian Ocean sea surface temperatures (SSTs). Interdecadal monsoonal variability is characterized by stronger monsoons during the 1970s, and weaker monsoons plus an increased prevalence of drier states in the later part of the record. Stochastic simulations of daily rainfall occurrence and amount at the 11 stations are generated by introducing predictors based on large-scale precipitation from (a) reanalysis data, (b) an atmospheric general circulation model (GCM) run with observed SST forcing and (c) antecedent June–August Pacific SST anomalies. The reanalysis large-scale precipitation yields relatively accurate station-level simulations of the interannual variability of daily rainfall amount and occurrence, with rainfall intensity less well simulated. At some stations, interannual variations in 10-day dry-spell frequency are also simulated reasonably well. The interannual quality of the simulations is markedly degraded when the GCM simulations are used as inputs, while antecedent Pacific SST inputs yield an anomaly correlation skill comparable to that of the GCM

Note and Comment

Including Breach of Contract--Lumley V. Gye; Vote by machine is a Constitutional Ballot; Administration Upon Estates of Absentees; A Labor Union\u27s Right to Declare and Carry Out a Boycot

Coupled evolution of nitrogen cycling and redoxcline dynamics on the Yangtze Block across the Ediacaran-Cambrian transition

The authors acknowledge funding support from the NSF FESD and Earth-Life Transitions programs (T.L.), the NASA Astrobiology Institute under Cooperative Agreement No. NNA15BB03A issued through the Science Mission Directorate (T.L.), the key project of the Natural Science Foundation of China (C.-F.C.) (No. 41730424), and the program of China Scholarships Council (Y.C.) (No. 201504910582). Nitrogen and carbon isotope analyses were funded by startup funds from Virginia Tech to B.C.G.The Ediacaran-Cambrian transition is characterized by the evolution of complex eukaryotes and rapid diversification of metazoans. However, linkages between environmental triggers and evolutionary patterns remain unclear. Here, we present high-resolution records of carbon and nitrogen isotopic data (δ13C, δ15N) for a drill core extending from the early Ediacaran Doushantuo Formation to the early Cambrian Jiumenchong Formation, located on the slope of the Yangtze Block. Our data show that sedimentary bulk nitrogen isotope values (δ15Nbulk) decrease progressively from the early Ediacaran to the early Cambrian, broadly concurrent with nitrogen isotope data from other sections throughout the Yangtze Block. During the early Ediacaran, however, δ15Nbulk values from our study are higher (maximum 11.2‰) compared to those from more restricted coeval sections, suggesting a higher degree of denitrification in our slope section. The early Ediacaran δ15Nbulk data from the Yangtze Block may thus provide indirect evidence for an upwelling system that led to a shallower redoxcline in slope environments of the Upper Yangtze region. Widespread light δ15Nbulk values from the early Cambrian (minimum −7.5‰) paired with excess silicate-bound nitrogen throughout much of the Yangtze Block are most parsimoniously interpreted as non-quantitative assimilation of ammonium (NH4+) with relatively high concentrations of NH4+ accumulating in the deep basin. Overall, the spatial and temporal trends in nitrogen cycling across the Yangtze Block suggest that fixed nitrogen was more bioavailable in the Ediacaran-Cambrian Yangtze Basin compared to previously studied Mesoproterozoic sections, although nitrogen speciation in the photic zone may have varied with time. Environmental factors such as oxygen levels and nitrogen bioavailability may have shaped the evolutionary trajectory of life on the Yangtze Block and potentially elsewhere across the Ediacaran-Cambrian transition.PostprintPeer reviewe