The mechanism controlling the development of dopaminergic (DA) and serotonergic (5HT) neurons in vertebrates is not well understood. Here we characterized a zebrafish mutant--too few (tof)--that develops hindbrain 5HT and noradrenergic neurons, but does not develop hypothalamic DA and 5HT neurons. tof encodes a forebrain-specific zinc finger transcription repressor that is homologous to the mammalian Fezl (forebrain embryonic zinc finger-like protein). Mosaic and co-staining analyses showed that fezl was not expressed in DA or 5HT neurons and instead controlled development of these neurons non-cell-autonomously. Both the eh1-related repressor motif and the second zinc finger domain were necessary for tof function. Our results indicate that tof/fezl is a key component in regulating the development of monoaminergic neurons in the vertebrate brain.
Pain and cachexia are two of the most debilitating aspects of rheumatoid arthritis. Despite that, the mechanisms by which they are mediated are not well understood. We provide evidence that nerve growth factor (NGF), a secreted regulatory protein that controls neuronal survival during development, is a key mediator of pain and weight loss in auto-immune arthritis. Function blocking antibodies to NGF completely reverse established pain in rats with fully developed arthritis despite continuing joint destruction and inflammation. Likewise, these antibodies reverse weight loss while not having any effect on levels of the pro-cachectic agent tumor necrosis factor (TNF). Taken together, these findings argue that pathological joint pain and joint destruction are mechanistically independent processes and that NGF regulates an alternative cachexia pathway that is independent or downstream of TNF.
Children are the most frequent victims of dog bites presenting to hospital emergency departments (ED), but there are gaps in understanding of the circumstances of such bites. The objective of this study was to characterise the behavioural circumstances of dog bites by interviewing children ≤17 years (or parent proxies for children ≤6 years) presenting with dog bite injuries to The Children's Hospital of Philadelphia about the bite incident, its setting and associated interactions. Of 203 children enrolled, 51% were <7 years old and 55% were male. 72% of children knew the biting dog. Most bites to younger children occurred during positive interactions, initiated by the child, with stationary, familiar dogs, indoors. Most older bitten children had been active (eg, outdoors), unfamiliar with the dog and not interacting. Whereas face bites predominated (70%) in the younger group (<7 years), bites to extremities predominated (72%) in the older group. Recognition of the two distinctive behavioural and circumstantial subgroups of dog bites that emerged can lead to more effective prevention strategies.
In vertebrate embryos, spinal motor neurons project through segmentally reiterated nerves into the somites. Here, we report that zebrafish secondary motor neurons, which are similar to motor neurons in birds and mammals, depend on myotomal cues to navigate into the periphery. We show that the absence of myotomal adaxial cells in you-too/gli2 embryos severely impairs secondary motor axonal pathfinding, including their ability to project into the somites. Moreover, in diwanka mutant embryos, in which adaxial cells are present but fail to produce cues essential for primary motor growth cones to pioneer into the somites, secondary motor axons display similar pathfinding defects. The similarities between the axonal defects in you-too/gli2 and diwanka mutant embryos strongly suggest that pathfinding of secondary motor axons depends on myotome-derived cues, and that the diwanka gene is a likely candidate to produce or encode such a cue. Our experiments also demonstrate that diwanka plays a central role in the migration of primary and secondary motor neurons, suggesting that both neural populations share mechanisms underlying axonal pathfinding. In summary, we provide compelling evidence that myotomal cells produce multiple signals to initiate and control the migration of spinal nerve axons into the somites.
Preservice elementary teachers should experience science through inquiry in order to be effective in teaching science. In addition, inquiry as a mode of teaching is mandated by Kansas and National Science Education Standards. As a result of the No Child Left Behind Act, teachers also need to be prepared to include basic skills in reading and mathematics in all instruction. To address these issues, Fort Hays State University (FHSU) is adapting and extending the NSF-developed teacher enhancement materials Operation Primary Physical Science (OPPS) for use in a physical science course for preservice elementary teachers. This paper presents main features of OPPS, describes advantages of using it as a template in developing desired course material and discusses results collected with students enrolled in the adapted course during 2004/2005 academic year .
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