Does Epileptiform Activity Represent a Failure of Neuromodulation to Control Central Pattern Generator-Like Neocortical Behavior?

Rhythmic motor patterns in invertebrates are often driven by specialized "central pattern generators" (CPGs), containing small numbers of neurons, which are likely to be "identifiable" in one individual compared with another. The dynamics of any particular CPG lies under the control of modulatory substances, amines, or peptides, entering the CPG from outside it, or released by internal constituent neurons; consequently, a particular CPG can generate a given rhythm at different frequencies and amplitudes, and perhaps even generate a repertoire of distinctive patterns. The mechanisms exploited by neuromodulators in this respect are manifold: Intrinsic conductances (e.g., calcium, potassium channels), conductance state of postsynaptic receptors, degree of plasticity, and magnitude and kinetics of transmitter release can all be affected. The CPG concept has been generalized to vertebrate motor pattern generating circuits (e.g., for locomotion), which may contain large numbers of neurons - a construct that is sensible, if there is enough redundancy: that is, the large number of neurons consists of only a small number of classes, and the cells within any one class act stereotypically. Here we suggest that CPG and modulator ideas may also help to understand cortical oscillations, normal ones, and particularly transition to epileptiform pathology. Furthermore, in the case illustrated, the mechanism of the transition appears to be an exaggerated form of a normal modulatory action used to influence sensory processing

Evidence of exposure to Rickettsia felis in Australian patients

AbstractRickettsia felis is an emerging zoonosis, causing flea-borne spotted fever (FBSF). Serological diagnosis is typically confounded by cross-reactivity with typhus group rickettsiae and prior to the development of specific serological methods, cases of FBSF in Australia were misdiagnosed.Patient sera tested between August 2010 and December 2013 and known to be seropositive to R. typhi by immunofluorescence antibody testing (IFAT) were subsequently retested against R. felis using an R. felis-specific IFAT. Sera of 49 patients were of a sufficient quality to be included in re-analysis. A classification of FBSF and murine typhus (MT) was attributed to fourteen and seven patients respectively, based on a minimum four-fold higher antibody titre to R. felis than to R. typhi and vice versa. Twenty-eight patients were classified as indeterminate for either R. felis or R. typhi (antibody titres within two-fold of one another).Historically, it is likely that Australian patients clinically ill with FBSF were misdiagnosed. It is important that medical practitioners consider FBSF as part of their differential diagnoses, and obtain relevant history with regard to patient's exposure to domestic pets and their fleas. Australian microbiology diagnostic laboratories should include serological testing for R. felis as part of the diagnostic panel for febrile diseases. Veterinarians are encouraged to increase their awareness of this emerging zoonosis and advocate flea control in pets

Exploring the financial and investment implications of the Paris Agreement

A global energy transition is underway. Limiting warming to 2°C (or less), as envisaged in the Paris Agreement, will require a major diversion of scheduled investments in the fossil-fuel industry and other high-carbon capital infrastructure towards renewables, energy efficiency, and other low or negative carbon technologies. The article explores the scale of climate finance and investment needs embodied in the Paris Agreement. It reveals that there is little clarity in the numbers from the plethora of sources (official and otherwise) on climate finance and investment. The article compares the US$100 billion target in the Paris Agreement with a range of other financial metrics, such as investment, incremental investment, energy expenditure, energy subsidies, and welfare losses. While the relatively narrowly defined climate finance included in the US$100 billion figure is a fraction of the broader finance and investment needs of climate-change mitigation and adaptation, it is significant when compared to some estimates of the net incremental costs of decarbonization that take into account capital and operating cost savings. However, even if the annual US$100 billion materializes, achieving the much larger implied shifts in investment will require the enactment of long-term internationally coordinated policies, far more stringent than have yet been introduced.</i

Iteration functions re-visited

Two classes of Iteration Functions (IFs) are derived in this paper. The first (one-point IFs) was originally derived by Joseph Traub using a different approach to ours (simultaneous IFs). The second is new and is demonstrably shown to be more informationally efficient than the first. These IFs apply to polynomials with arbitrary complex coefficients and zeros, which can also be multiple

The Exoplanet Microlensing Survey by the Proposed WFIRST Observatory

The New Worlds, New Horizons report released by the Astronomy and Astrophysics Decadal Survey Board in 2010 listed the Wide Field Infrared Survey Telescope (WFIRST) as the highest-priority large space mission for the . coming decade. This observatory will provide wide-field imaging and slitless spectroscopy at near infrared wavelengths. The scientific goals are to obtain a statistical census of exoplanets using gravitational microlensing. measure the expansion history of and the growth of structure in the Universe by multiple methods, and perform other astronomical surveys to be selected through a guest observer program. A Science Definition Team has been established to assist NASA in the development of a Design Reference Mission that accomplishes this diverse array of science programs with a single observatory. In this paper we present the current WFIRST payload concept and the expected capabilities for planet detection. The observatory. with science goals that are complimentary to the Kepler exoplanet transit mission, is designed to complete the statistical census of planetary systems in the Galaxy, from habitable Earth-mass planets to free floating planets, including analogs to all of the planets in our Solar System except Mercury. The exoplanet microlensing survey will observe for 500 days spanning 5 years. This long temporal baseline will enable the determination of the masses for most detected exoplanets down to 0.1 Earth masses

Locomotor rhythm maintenance: electrical coupling among premotor excitatory interneurons in the brainstem and spinal cord of young Xenopus tadpoles

Electrical coupling is important in rhythm generating systems. We examine its role in circuits controlling locomotion in a simple vertebrate model, the young Xenopus tadpole, where the hindbrain and spinal cord excitatory descending interneurons (dINs) that drive and maintain swimming have been characterised. Using simultaneous paired recordings, we show that most dINs are electrically coupled exclusively to other dINs (DC coupling coefficients ∼8.5%). The coupling shows typical low-pass filtering. We found no evidence that other swimming central pattern generator (CPG) interneurons are coupled to dINs or to each other. Electrical coupling potentials between dINs appear to contribute to their unusually reliable firing during swimming. To investigate the role of electrical coupling in swimming, we evaluated the specificity of gap junction blockers (18-β-GA, carbenoxolone, flufenamic acid and heptanol) in paired recordings. 18-β-GA at 40–60 μm produced substantial (84%) coupling block but few effects on cellular properties. Swimming episodes in 18-β-GA were significantly shortened (to ∼2% of control durations). At the same time, dIN firing reliability fell from nearly 100% to 62% of swimming cycles and spike synchronization weakened. Because dINs drive CPG neuron firing and are critical in maintaining swimming, the weakening of dIN activity could account for the effects of 18-β-GA on swimming. We conclude that electrical coupling among pre motor reticulospinal and spinal dINs, the excitatory interneurons that drive the swimming CPG in the hatchling Xenopus tadpole, may contribute to the maintenance of swimming as well as synchronization of activity