Phosphorylation of Glutamine Synthetase on Threonine 301 Contributes to Its Inactivation During Epilepsy

The astrocyte-specific enzyme glutamine synthetase (GS), which catalyzes the amidation of glutamate to glutamine, plays an essential role in supporting neurotransmission and in limiting NH4+ toxicity. Accordingly, deficits in GS activity contribute to epilepsy and neurodegeneration. Despite its central role in brain physiology, the mechanisms that regulate GS activity are poorly defined. Here, we demonstrate that GS is directly phosphorylated on threonine residue 301 (T301) within the enzyme’s active site by cAMP-dependent protein kinase (PKA). Phosphorylation of T301 leads to a dramatic decrease in glutamine synthesis. Enhanced T301 phosphorylation was evident in a mouse model of epilepsy, which may contribute to the decreased GS activity seen during this trauma. Thus, our results highlight a novel molecular mechanism that determines GS activity under both normal and pathological conditions.</p

Persistent physical symptoms reduction intervention: a system change and evaluation in secondary care (PRINCE secondary) - a CBT-based transdiagnostic approach: study protocol for a randomised controlled trial

Background: Persistent physical symptoms (PPS), also known as medically unexplained symptoms (MUS), affect approximately 50% of patients in secondary care and are often associated with disability, psychological distress and increased health care costs. Cognitive behavioural therapy (CBT) has demonstrated both shortand long-term efficacy with small to medium effect sizes for PPS, with larger treatment effects for specific PPS syndromes, including non-cardiac chest pain, irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS). Research indicates that PPS conditions share similar cognitive and behavioural responses to symptoms, such as avoidance and unhelpful beliefs. This suggests that a transdiagnostic approach may be beneficial for patients with PPS. Methods: A randomised controlled trial (RCT) will be conducted to evaluate the efficacy and costeffectiveness of a transdiagnostic CBT-based intervention for PPS. 322 participants with PPS will be recruited from secondary care clinics. Participants stratified by clinic and disability level will be randomised to CBT plus standard medical care (SMC) versus SMC alone. The intervention consists of 8 CBT sessions delivered by a qualified therapist over a period of 20 weeks. Outcomes will be assessed at 9, 20, 40- and 52-weeks post randomisation. Efficacy will be assessed by examining the difference between arms in the primary outcome Work and Social Adjustment Scale (WSAS) at 52 weeks after randomisation. Secondary outcomes will include mood, symptom severity and clinical global impression at 9, 20, 40 and 52 weeks. Cost-effectiveness will be evaluated by combining measures of health service use, informal care, loss of working hours and financial benefits at 52 weeks. Discussion: This trial will provide a powered evaluation of the efficacy and cost-effectiveness of a transdiagnostic CBT approach versus SMC for patients with PPS. It will also provide valuable information about potential healthcare pathways for patients with PPS within the National Health Service (NHS). Trial registration: ClinicalTrials.gov NCT02426788. Registered 27 April 2015. Overall trial status: Ongoing; Recruitment status: No longer recruiting

Impact of time-dependent non-axisymmetric velocity perturbations on dynamo action of von-K\'arm\'an-like flows

We have performed numerical simulations of the kinematic induction equation in order to examine the dynamo efficiency of an axisymmetric von-K\'arm\'an-like flow subject to time-dependent non-axisymmetric velocity perturbations. The numerical model is based on the setup of the French Von-K\'arm\'an-Sodium dynamo (VKS) and on the flow measurements from a model water experiment conducted at the University of Navarra in Pamplona, Spain. Our simulations show that the interactions of azimuthally drifting flow perturbations with the fundamental drift of the magnetic eigenmode (caused by the inevitable equatorial symmetry breaking of the basic flow) essentially determine the temporal behavior of the dynamo state. We find two distinct regimes of dynamo action that depend on the (prescribed) drift frequency of an ($m=2$) vortex-like flow perturbation. For comparatively slowly drifting vortices we observe a narrow window with enhanced growth-rates and a drift of the magnetic eigenmode that is synchronized with the perturbation drift. The resonance-like enhancement of the growth-rates takes place when the vortex drift frequency roughly equals the drift frequency of the magnetic eigenmode in the unperturbed system. Outside of this small window, the field generation is hampered compared to the unperturbed case, and the field amplitude of the magnetic eigenmode is modulated with approximately twice the vortex drift frequency. The abrupt transition between the resonant regime and the modulated regime is identified as an spectral exceptional point where eigenvalues (growth-rates and frequencies) and eigenfunctions of two previously independent modes collapse.Comment: 14 pages, 14 Figures. Minor changes to match the published versio

Measuring the impacts of the national flood insurance program

The National Flood Insurance Program was established in 1968 as a federally administered insurance program to reduce costs to the federal government for flood recovery and allocate recovery costs among potential disaster relief beneficiaries. Participants purchase flood insurance through participating property insurance providers which receive a haircut of the premium for overhead costs and passes the remainder to the Federal Emergency Management Agency. This paper outlines a model to measure the net social benefits attributable to the insurance component of the NFIP. Development of this model provides the baseline for further economic and social analysis of the NFIP

How Biology Became Social and What It Means for Social Theory

In this paper I first offer a systematic outline of a series of conceptual novelties in the life-sciences that have favoured, over the last three decades, the emergence of a more social view of biology. I focus in particular on three areas of investigation: (1) technical changes in evolutionary literature that have provoked a rethinking of the possibility of altruism, morality and prosocial behaviours in evolution; (2) changes in neuroscience, from an understanding of the brain as an isolated data processor to the ultrasocial and multiply connected social brain of contemporary neuroscience; and (3) changes in molecular biology, from the view of the gene as an autonomous master of development to the ‘reactive genome’ of the new emerging field of molecular epigenetics. In the second section I reflect on the possible implications for the social sciences of this novel biosocial terrain and argue that the postgenomic language of extended epigenetic inheritance and blurring of the nature/nurture boundaries will be as provocative for neo-Darwinism as it is for the social sciences as we have known them. Signs of a new biosocial language are emerging in several social-science disciplines and this may represent an exciting theoretical novelty for twenty-first social theory

The PHENIX Experiment at RHIC

The physics emphases of the PHENIX collaboration and the design and current status of the PHENIX detector are discussed. The plan of the collaboration for making the most effective use of the available luminosity in the first years of RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program available at http://www.rhic.bnl.gov/phenix

Apercal-The Apertif calibration pipeline

Apertif (APERture Tile In Focus) is one of the Square Kilometre Array (SKA) pathfinder facilities. The Apertif project is an upgrade to the 50-year-old Westerbork Synthesis Radio Telescope (WSRT) using phased-array feed technology. The new receivers create 40 individual beams on the sky, achieving an instantaneous sky coverage of 6.5 square degrees. The primary goal of the Apertif Imaging Survey is to perform a wide survey of 3500 square degrees (AWES) and a medium deep survey of 350 square degrees (AMES) of neutral atomic hydrogen (up to a redshift of 0.26), radio continuum emission and polarisation. Each survey pointing yields 4.6 TB of correlated data. The goal of Apercal is to process this data and fully automatically generate science ready data products for the astronomical community while keeping up with the survey observations. We make use of common astronomical software packages in combination with Python based routines and parallelisation. We use an object oriented module-based approach to ensure easy adaptation of the pipeline. A Jupyter notebook based framework allows user interaction and execution of individual modules as well as a full automatic processing of a complete survey observation. If nothing interrupts processing, we are able to reduce a single pointing survey observation on our five node cluster with 24 physical cores and 256 GB of memory each within 24 h keeping up with the speed of the surveys. The quality of the generated images is sufficient for scientific usage for 44% of the recorded data products with single images reaching dynamic ranges of several thousands. Future improvements will increase this percentage to over 80%. Our design allowed development of the pipeline in parallel to the commissioning of the Apertif system

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal