CNS Hypomyelination Disrupts Axonal Conduction and Behavior in Larval Zebrafish.

Myelination is essential for central nervous system (CNS) formation, health and function. As a model organism, larval zebrafish have been extensively employed to investigate the molecular and cellular basis of CNS myelination, because of their genetic tractability and suitability for non-invasive live cell imaging. However, it has not been assessed to what extent CNS myelination affects neural circuit function in zebrafish larvae, prohibiting the integration of molecular and cellular analyses of myelination with concomitant network maturation. To test whether larval zebrafish might serve as a suitable platform with which to study the effects of CNS myelination and its dysregulation on circuit function, we generated zebrafish myelin regulatory factor (myrf) mutants with CNS-specific hypomyelination and investigated how this affected their axonal conduction properties and behavior. We found that myrf mutant larvae exhibited increased latency to perform startle responses following defined acoustic stimuli. Furthermore, we found that hypomyelinated animals often selected an impaired response to acoustic stimuli, exhibiting a bias toward reorientation behavior instead of the stimulus-appropriate startle response. To begin to study how myelination affected the underlying circuitry, we established electrophysiological protocols to assess various conduction properties along single axons. We found that the hypomyelinated myrf mutants exhibited reduced action potential conduction velocity and an impaired ability to sustain high-frequency action potential firing. This study indicates that larval zebrafish can be used to bridge molecular and cellular investigation of CNS myelination with multiscale assessment of neural circuit function.SIGNIFICANCE STATEMENT Myelination of CNS axons is essential for their health and function, and it is now clear that myelination is a dynamic life-long process subject to modulation by neuronal activity. However, it remains unclear precisely how changes to myelination affects animal behavior and underlying action potential conduction along axons in intact neural circuits. In recent years, zebrafish have been employed to study cellular and molecular mechanisms of myelination, because of their relatively simple, optically transparent, experimentally tractable vertebrate nervous system. Here we find that changes to myelination alter the behavior of young zebrafish and action potential conduction along individual axons, providing a platform to integrate molecular, cellular, and circuit level analyses of myelination using this model.

Anaerobic sulphate-reducing microbial process using UASB reactor for heavy metals decontamination.

This study was conducted to investigate the possibility of using sewage as an organic substrate for the growth of sulphate reducing bacteria (SRB) and to acclimatise anaerobic sludge to produce sulphide from sulphate reduction, with a view to metal precipitation. The experiments were carried out in a continuous bench-scale bioreactor (13 1 UASB reactor) operated with hydraulic retention times (HRT) of 11 and 19 hours. The feed solution used was composed of the liquid part of the sewage (organic matter) supplemented with nickel sulphate and sodium sulphate. The results showed that it was possible to acclimatise anaerobic sludge for production of sulphide by sulphate reduction. A relation between the available COD and the concentration of sulphate reduced by SRB was observed. High nickel removal efficiency (96%) was obtained during the whole operation (320 days). However, the process required very strict control of the organic load available (sewage) in the solution and, if necessary, the addition of a complementary organic carbon source, in order to maintain a constant level of metal removal. The SRB were not affected by the HRT values studied and were installed and maintained in the system; however, granular sludge was not observed. The micrographs confirmed the presence of iron and nickel sulphides and also a mixed bacterial culture in the anaerobic sludge. The EDS spectrum of the sludge showed that nickel was retained in the sludge predominantly as a nickel sulphide.

Potential pitfall in parathyroid sestamibi imaging resulting from a cardiac pacemaker.

A 47-year-old woman with a history of end-stage renal disease and hyperparathyroidism after total parathyroidectomy had Tc-99m sestamibi imaging to identify possible ectopic parathyroid tissue. This study was prompted by increasing calcium and parathyroid hormone levels after several years of taking calcium supplements necessitated by a surgically induced hypoparathyroid state and end-stage renal disease. The scan showed persistent linear activity in the upper right mediastinum in delayed images, after washout of the thyroid had occurred. Because of the unusual configuration of this finding, investigation of the patient's clinical history and other imaging studies was undertaken. The authors concluded that the unusual mediastinal uptake was not hyperactive parathyroid tissue, but rather was attributed to the presence of central venous pacemaker wires. Thus, this case illustrates a potential pitfall in parathyroid sestamibi imaging, the uptake of which may increase in the presence of a cardiac pacemaker, and it emphasizes the importance of correlative imaging.

Genetic analysis of vertebrate sensory hair cell mechanosensation: the zebrafish circler mutants.

The molecular basis of sensory hair cell mechanotransduction is largely unknown. In order to identify genes that are essential for mechanosensory hair cell function, we characterized a group of recently isolated zebrafish motility mutants. These mutants are defective in balance and swim in circles but have no obvious morphological defects. We examined the mutants using calcium imaging of acoustic-vibrational and tactile escape responses, high resolution microscopy of sensory neuroepithelia in live larvae, and recordings of extracellular hair cell potentials (microphonics). Based on the analyses, we have identified several classes of genes. Mutations in sputnik and mariner affect hair bundle integrity. Mutant astronaut and cosmonaut hair cells have relatively normal microphonics and thus appear to affect events downstream of mechanotransduction. Mutant orbiter, mercury, and gemini larvae have normal hair cell morphology and yet do not respond to acoustic-vibrational stimuli. The microphonics of lateral line hair cells of orbiter, mercury, and gemini larvae are absent or strongly reduced. Therefore, these genes may encode components of the transduction apparatus.