Coupled ocean–atmosphere interactions between the Madden–Julian oscillation and synoptic-scale variability over the warm pool

A principal component analysis of the combined fields of sea surface temperature (SST) and surface zonal and meridional wind reveals the dominant mode of intraseasonal (30-70-day) co-variability during northern winter in the tropical Eastern Hemisphere is that of the Madden-Julian Oscillation (MJO). Regression calculations show that the submonthly (30-day high-pass filtered) surface wind variability is significantly modulated during the MJO. Regions of increased (decreased) submonthly surface wind variability propagate eastward, approximately in phase with the intraseasonal surface westerly (easterly) anomalies of the MJO. Due to the dependence of the surface latent heat flux on the magnitude of the total wind speed, this systematic modulation of the submonthly surface wind variability produces a significant component in the intraseasonal latent heat flux anomalies, which partially cancels the latent heat flux anomalies due to the slowly varying intraseasonal wind anomalies, particularly south of 10S. A method is derived that demodulates the submonthly surface wind variability from the slowly varying intraseasonal wind anomalies. This method is applied to the wind forcing fields of a one-dimensional ocean model. The model response to this modified forcing produces larger intraseasonal SST anomalies than when the model is forced with the observed forcing over large areas of the southwest Pacific Ocean and southeast Indian Ocean during both phases of the MJO. This result has implications for accurate coupled modeling of the MJO. A similar calculation is applied to the surface shortwave flux, but intraseasonal modulation of submonthly surface shortwave flux variability does not appear to be important to the dynamics of the MJO

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)