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)

Targeted management intervention reduces rate of population decline of Corn Buntings Emberiza calandra in eastern Scotland

Aims To determine whether targeted management intervention helps to halt or reverse the decline of Corn Buntings in eastern Scotland. Methods Counts of territorial male Corn Buntings in the breeding seasons of 2002 and 2004 were compared across 53 2-km squares. Nineteen of these were subject to management intervention designed to benefit Corn Buntings, effective from 2003. The other 34 had no such management. For a subset of 44 tetrads, counts in 2000 and 2002 were also compared between the two sets of tetrads. Results Between 2002 and 2004, Corn Bunting numbers showed no significant change in tetrads with targeted management intervention, but declined by 43% in tetrads with no intervention. By contrast, population changes did not differ significantly in these two groups of tetrads between 2000 and 2002, before management was implemented. Conclusion Targeted management intervention was associated with reduced short-term probability of Corn Bunting population decline on farms in eastern Scotland. Management interventions that are designed to provide habitats required by the species have the potential to halt, or perhaps reverse, the Corn Bunting decline in eastern Scotland

Crop sward structure explains seasonal variation in nest site selection and informs agri-environment scheme design for a species of high conservation concern: the Corn Bunting <i>Emberiza calandra</i>

<div><p><b>Capsule</b> Corn Buntings nested in tall dense grasses and cereals, selecting for sward density over height, and cereal fields with high weed scores.</p><p><b>Aims</b> To measure the vegetation attributes of fields selected as nest sites by Corn Buntings, to inform the design of safe nesting habitat measures in agri-environment schemes for this rapidly declining ground-nesting passerine.</p><p><b>Methods</b> Nesting activity was monitored across 32 farms in eastern Scotland during 2004–09. Land use and singing males were mapped to measure habitat availability for nesting females within their mate's territory, and crop swards measured. Effects of sward characteristics on field selection for nesting, and seasonal variation in crop use, were modelled.</p><p><b>Results</b> Nests (95% of 580) were mainly in cereals and grasses. Taller denser swards were selected, with sward density a stronger predictor of field use than sward height, and cereal field use strongly associated with high weed scores. Variation in sward structure between crop types, and changes due to crop maturation or harvesting, largely explained seasonal patterns in crop use.</p><p><b>Conclusion</b> Conservation measures targeting nesting Corn Buntings should provide uncut or late-cut grasses or cereals 30–100 cm tall with a dense ground layer of weeds or crop vegetation.</p></div

Decline of Corn Buntings Emberiza calandra on east Scottish study areas in 1989-2007

Capsule Adult numbers on many study areas fluctuated from year to year, but overall showed a large decline, down to extinction on most areas. Aims To measure changes in summer numbers of adult Corn Buntings in a large sample of study areas holding discrete localized populations. Methods Singing cocks and hens paired with them were counted in early summer at 30 study areas on farmland from south Angus to central Aberdeenshire. Sixteen populations occurring throughout 1989-95 were called 'groups'. Counts also included 16 cases where a new 'offshoot' appeared in late May or the start of June, not having been seen earlier in that spring or in the previous winter or summer. Results Following relative stability in 1989-95, large declines occurred in 1995-96, 1998-99 and 2003-04, and decreases far outweighed occasional increases between consecutive summers. The numbers of established groups, new offshoots, and older offshoots all declined with the year. Although containing one to nine founding pairs, new offshoots became extinct later, in six cases after one summer. No new offshoot was seen after 1995. Conclusions Although 22 study areas held birds in 1989 and 25 in 1990, this fell to 10 in 1999, seven in 2005, and four in 2007 (the only areas that held birds in all years). On all areas combined, cock numbers fell by 83% between 1989 and 2007. Targeted implementation of appropriate agri-environment measures is urgently needed to halt and reverse such declines, a challenge made all the greater within the last year by rising grain prices, delays to the introduction of new measures, and abolition of EU 'set-aside' as a means for providing food and nesting habitat