Guanidinoacetate methyltransferase (GAMT) deficiency: a rare but treatable epilepsy

Epilepsy commonly presents in childhood as part of a syndrome, and some such children may reach adult services without an underlying syndromic diagnosis. For adult neurologists taking over their care, it is often unclear how hard to search for an underlying diagnosis. The diagnostic yield may be small and such a diagnosis may not change management. Young adults with learning difficulties are also challenging to investigate, as they may not tolerate standard epilepsy tests.We present such a case in which simple tests identified a unifying diagnosis. With the new diagnosis came a new treatment that had a significant impact on seizures and quality of life

Assessing availability and greenhouse gas emissions of lignocellulosic biomass feedstock supply – case study for a catchment in England

© 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.Feedstocks from lignocellulosic biomass (LCB) include crop residues and dedicated per¬ennial biomass crops. The latter are often considered superior in terms of climate change mitigation potential. Uncertainty remains over their availability as feedstocks for biomass provision and the net greenhouse gas emissions (GHG) during crop production. Our objective was to assess the optimal land allocation to wheat and Miscanthus in a specific case study located in England, to increase bio¬mass availability, improve the carbon balance (and reduce the consequent GHG emissions), and mini¬mally constrain grain production losses from wheat. Using soil and climate variables for a catchment in east England, biomass yields and direct nitrogen emissions were simulated with validated process-based models. A ‘Field to up-stream factory gate’ life-cycle assessment was conducted to estimate indirect management-related GHG emissions. Results show that feedstock supply from wheat straw can be supplemented beneficially with LCB from Miscanthus grown on selected low-quality soils. In our study, 8% of the less productive arable land area was dedicated to Miscanthus, increasing total LCB provision by about 150%, with a 52% reduction in GHG emission per ton LCB delivered and only a minor effect on wheat grain production (−3%). In conclusion, even without considering the likely carbon sequestration in impoverished soils, agriculture should embrace the opportunities to provide the bioeconomy with LCB from dedicated, perennial crops.Peer reviewe

PI3K/mTORC2 regulates TGF-β/Activin signalling by modulating Smad2/3 activity via linker phosphorylation

Crosstalk between the phosphatidylinositol 3-kinase (PI3K) and the transforming growth factor-β signalling pathways play an important role in regulating many cellular functions. However, the molecular mechanisms underpinning this crosstalk remain unclear. Here, we report that PI3K signalling antagonizes the Activin-induced definitive endoderm (DE) differentiation of human embryonic stem cells by attenuating the duration of Smad2/3 activation via the mechanistic target of rapamycin complex 2 (mTORC2). Activation of mTORC2 regulates the phosphorylation of the Smad2/3-T220/T179 linker residue independent of Akt, CDK and Erk activity. This phosphorylation primes receptor-activated Smad2/3 for recruitment of the E3 ubiquitin ligase Nedd4L, which in turn leads to their degradation. Inhibition of PI3K/mTORC2 reduces this phosphorylation and increases the duration of Smad2/3 activity, promoting a more robust mesendoderm and endoderm differentiation. These findings present a new and direct crosstalk mechanism between these two pathways in which mTORC2 functions as a novel and critical mediator

Cellular structure of qq-Brauer algebras

In this paper we consider the $q$-Brauer algebra over $R$ a commutative noetherian domain. We first construct a new basis for $q$-Brauer algebras, and we then prove that it is a cell basis, and thus these algebras are cellular in the sense of Graham and Lehrer. In particular, they are shown to be an iterated inflation of Hecke algebras of type $A_{n-1}.$ Moreover, when $R$ is a field of arbitrary characteristic, we determine for which parameters the $q$-Brauer algebras are quasi-heredity. So the general theory of cellular algebras and quasi-hereditary algebras applies to $q$-Brauer algebras. As a consequence, we can determine all irreducible representations of $q$-Brauer algebras by linear algebra methods

Organic aerosol formation downwind from the Deepwater Horizon oil spill.

A large fraction of atmospheric aerosols are derived from organic compounds with various volatilities. A National Oceanic and Atmospheric Administration (NOAA) WP-3D research aircraft made airborne measurements of the gaseous and aerosol composition of air over the Deepwater Horizon (DWH) oil spill in the Gulf of Mexico that occurred from April to August 2010. A narrow plume of hydrocarbons was observed downwind of DWH that is attributed to the evaporation of fresh oil on the sea surface. A much wider plume with high concentrations of organic aerosol (>25 micrograms per cubic meter) was attributed to the formation of secondary organic aerosol (SOA) from unmeasured, less volatile hydrocarbons that were emitted from a wider area around DWH. These observations provide direct and compelling evidence for the importance of formation of SOA from less volatile hydrocarbons

Anti-Allergic Cromones Inhibit Histamine and Eicosanoid Release from Activated Human and Murine Mast Cells by Releasing Annexin A1

PMCID: PMC3601088This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

A global disorder of imprinting in the human female germ line

Imprinted genes are expressed differently depending on whether they are carried by a chromosome of maternal or paternal origin. Correct imprinting is established by germline-specific modifications; failure of this process underlies several inherited human syndromes. All these imprinting control defects are cis-acting, disrupting establishment or maintenance of allele-specific epigenetic modifications across one contiguous segment of the genome. In contrast, we report here an inherited global imprinting defect. This recessive maternal-effect mutation disrupts the specification of imprints at multiple, non-contiguous loci, with the result that genes normally carrying a maternal methylation imprint assume a paternal epigenetic pattern on the maternal allele. The resulting conception is phenotypically indistinguishable from an androgenetic complete hydatidiform mole, in which abnormal extra-embryonic tissue proliferates while development of the embryo is absent or nearly so. This disorder offers a genetic route to the identification of trans-acting oocyte factors that mediate maternal imprint establishment

Participation and satisfaction after spinal cord injury: results of a vocational and leisure outcome study

Study design: Survey. Objectives: Insight in (1) the changes in participation in vocational and leisure activities and (2) satisfaction with the current participation level of people with spinal cord injuries (SCIs) after reintegration in society. Design: Descriptive analysis of data from a questionnaire. Setting: Rehabilitation centre with special department for patients with SCIs, Groningen, The Netherlands. Subjects: A total of 57 patients with traumatic SCI living in the community, who were admitted to the rehabilitation centre two to 12 years before the current assessment. Main outcome measures: Changes in participation in activities; current life satisfaction; support and unmet needs. Results: Participation expressed in terms of hours spent on vocational and leisure activities changed to a great extent after the SCI. This was mainly determined by a large reduction of hours spent on paid work. While 60% of the respondents successfully reintegrated in work, many changes took place in the type and extent of the job. Loss of work was partially compensated with domestic and leisure activities. Sports activities were reduced substantially. The change in participation level and compensation for the lost working hours was not significantly associated with the level of SCI-specific health problems and disabilities. As was found in other studies, most respondents were satisfied with their lives. Determinants of a negative life satisfaction several years following SCI were not easily indicated. Reduced quality of life was particularly related to an unsatisfactory work and leisure situation. Conclusions: Most people with SCI in this study group were able to resume work and were satisfied with their work and leisure situation