The folly of EU policy transfer: why the CAP does not fit Central and Eastern Europe (new revised title)

This paper assesses the appropriateness of the EU’s CAP for meeting rural development challenges in the New Member States (NMS). It argues that while the mitigation of structural problems confronting rural areas in these countries is critical to meeting the challenge of effectively integrating Central and Eastern Europe (CEE) into the EU, the CAP is poorly suited for four key reasons: (i) lack of convergence between the socio-economic conditions of rural areas in the NMS and EU15; (ii) differences in farm structures in terms of both size and organisational type; (iii) an inappropriate balance of resources between Pillars I and II; and (iv) inadequate capacity to implement rural development measures in NMS. Overall, the CAP was insufficiently reformed and represents a failure to adequately adjust from an exclusively western European institution into an appropriate pan-European organisation

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

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)

Models and Data for Mombaerts et al., "Dynamical Differential Expression (DyDE) Reveals the Period Control Mechanisms of the Arabidopsis Circadian Oscillator", PLOS Computational Biology, 2019.

This dataset consists of experimental data that reveals the period control mechanisms of the Arabidopsis Circadian Oscillator (as described in the associated publication) and is provided here in an XLSX file. MATLAB code for performing the dynamic differential expression (DyDe) described in the publication are provided as .ZI

Ultra-low noise PEDOT:PSS electrodes on bacterial cellulose: A sensor to access bioelectrical signals in non-electrogenic cells

This study is focused on the particular advantages of organic-based devices to measure cells that do not generate action potentials, also known as non-electrogenic cells. While there is a vast literature about the application of organic conductors to measure neurons, cardiomyocytes and brain tissues, electrical measurements of non-electrogenic cells are rare. This is because non-electrogenic cells generate weak signals with frequencies below 1 Hz. Designing low noise devices in a millihertz frequency range is extremely challenging due to the intrinsic thermal and 1/f type noise generated by the sensing electrode. Here, we demonstrate that the coating of cellulose nanofibers with conducting PEDOT:PSS ink allows the fabrication of a nanostructured surface that establishes a low electrical double-layer resistance with liquid solutions. The low interfacial resistance combined with the large effective sensing area of PEDOT:PSS electrodes minimizes the thermal noise and lowers the amplitude detection limit of the sensor. The electrode noise decreases with frequency from 548 nV r.m.s at 0.1 Hz to a minimum of 6 nV r.m.s for frequencies higher than 100 Hz. This low noise makes it possible to measure low frequency bioelectrical communication signals, typical of non-electrogenic cells, that have until now been difficult to explore using metallic-based microelectrode arrays. The performance of the PEDOT:PSS-based electrodes is demonstrated by recording signals generated by populations of glioma cells with a signal-to-noise ratio as high as 140.Portuguese Foundation for Science and Technology (FCT/MCTES)Portuguese Foundation for Science and TechnologyFEDER under the PT 2020 Partnership Agreement"Implantable organic devices for advanced therapies", INNOVATE [PTDC/EEIAUT/5442/2014]Instituto de Telecomunicacoes, IT [UIDB/EEA/50008/2020]Centro de Ciencias do Mar, CCMar [UIDB/Multi/04326/2020]CICECO -Aveiro Institute of Materials [UIDB/50011/2020, UIDP/50011/2020]FCT, under the "Norma Transit.oria" project CT0020 [DL57/2016/CP1361]FCTPortuguese Foundation for Science and TechnologyEuropean Commission [SFRH/BD/148688/2019]info:eu-repo/semantics/publishedVersio