Structures and biological activities of three synaptic antagonists from orb weaver spider venom

The venom of Argiope aurantia, an orb weaver spider, contains a mixture of low molecular weight "argiotoxins", which block neuromuscular transmission in insects. Complete structure elucidation of three argiotoxins reveals common features; a hydrophilic, basic domain of arginine, a polyamine and asparagine is connected to an aromatic moiety contributed either by 4-hydroxyindole-3-acetic acid or 2,4-dihydroxyphenylacetic acid. Structural assignments of two argiotoxins are verified by chemical synthesis. The argiotoxins cause reversible paralysis when injected into insects and this is correlated with a stimulus-dependent inhibition of skeletal neuromuscular transmission at submicromolar concentrations.     

Structures of paralytic acylpolyamines from the spider Agelenopsis aperta

The structures are given for five paralytic acylpolyamines from the venom of the funnel web spider, Agelenopsis aperta. The acyl moieties are derived from (3-indolyl)acetic acid, (4-hydroxy-3-indolyl)acetic acid, and 4-hydroxybenzoic acid. The polyamine portions of the toxins are novel. Three toxins (AG489, AG505, and AG452) contain 1, 5, 9, 13, 18, 22-hexaazadocosane which is unique as a natural polyamine because of its length and hydroxylation at the 5-aza position. The polyamine portions of two other alpha-agatoxins (AG488 and AG504) are unusual also, containing guanidinooxy moieties.     

Radiotherapy facilities,equipment, and staffing in Poland: 2005–2011

Background and purpose

To evaluate the current status of radiotherapy facilities, staffing, and equipment, treatment and patients in Poland for the years 2005–2011 following implementation of the National Cancer Programme.

Methods

A survey was sent to the radiotherapy centres in Poland to collect data on available equipment, staffing, and treatments in the years 2005–2011.

Results

In 2011, 76,000 patients were treated with radiotherapy at 32 centres vs. 63,000 patients at 23 centres in 2005. Number of patients increased by 21%. In 2011, there were 453 radiation oncologists – specialists (1 in 168 patients), 325 medical physicists (1 in 215 patients), and 883 radiotherapy technicians (1 in 86 patients) vs. 320, 188, and 652, respectively, in 2005. The number of linear accelerators increased by 60%, from 70 units in 2005 to 112 in 2011. The current linac/patient ratio in Poland is 1 linac per 678 patients. Waiting times from diagnosis to the start of treatment has decreased.

Conclusion

Compared to 2005, there are more treatment facilities, more and better equipment (linacs), and more cancer care specialists. There are still large differences between the 16 Polish provinces in terms of equipment availability and ease of access to treatment. However, radiotherapy services in Poland have improved dramatically since the year 2005.     

Intraflagellar transport genes are essential for differentiation and survival of vertebrate sensory neurons

Cilia play diverse roles in vertebrate and invertebrate sensory neurons. We show that a mutation of the zebrafish oval (ovl) locus affects a component of the ciliary transport (IFT) mechanism, the IFT88 polypeptide. In mutant retina, cilia are generated but not maintained, producing the absence of photoreceptor outer segments. A loss of cilia also occurs in auditory hair cells and olfactory sensory neurons. In all three sense organs, cilia defects are followed by degeneration of sensory cells. Similar phenotypes are induced by the absence of the IFT complex B polypeptides, ift52 and ift57, but not by the loss of complex A protein, ift140. The degeneration of mutant photoreceptor cells is caused, at least partially, by the ectopic accumulation of opsins. These studies reveal an essential role for IFT genes in vertebrate sensory neurons and implicate the molecular components of intraflagellar transport in degenerative disorders of these cells.     

Analysis of gene function in the zebrafish retina

Mutagenesis screens in zebrafish have uncovered several hundred mutant alleles affecting the development of the retina and established the zebrafish as one of the leading models of vertebrate eye development. In addition to forward genetic mutagenesis approaches, gene function in the zebrafish embryo is being studied using several reverse genetic techniques. Some of these rely on the overexpression of a gene product, others take advantage of antisense oligonucleotides to block function of selected loci. Here we describe these methods in the context of the developing eye.     

A screen for genetic defects of the zebrafish ear

To advance the understanding of genetic mechanisms involved in the patterning and the differentiation of the vertebrate auditory system, we screened for mutations affecting ear development in the zebrafish larva. Fifteen recessive mutant alleles have been isolated and analyzed. The phenotypes of these mutants involve abnormalities in ear morphology, otolith formation, or both processes in parallel. Among morphological defects, we found mutations affecting early patterning of the otic vesicle, the morphogenesis of semicircular canals, and the expansion of the ear lumen. The two most severe mutant phenotypes involve the absence of anterior and posterior cristae, as well as a severely misshapen morphology of the ear. In the category of otolith mutants, we found defects in otolith formation, growth, and shape. As it proved to be the case in past screening efforts of this type, these mutant lines represent an asset in the studies of molecular mechanisms that regulate vertebrate ear development.     

Genetic defects of pronephric cilia in zebrafish

Cilia play key roles in many aspects of embryogenesis and adult physiology in vertebrates. Past genetic screens in zebrafish identified numerous defects of ciliogenesis, including several mutations in the components of the intraflagellar transport machinery. In contrast to previous studies, here we describe a collection of mutants that affect subpopulations of cilia. Mutant embryos are characterized by a shortening and an abnormal movement of kidney cilia, and in one case also a reduction of cilia length in the Kupffer's vesicle. In contrast to that, the cilia of sensory neurons, including photoreceptor cells, hair cells, and olfactory sensory cells, appear grossly intact. Motility defects of pronephric cilia vary in mutant strains from complete paralysis to an increased frequency of movement, and are associated with left-right asymmetry defects. While ciliary ultrastructure is normal in most mutants, one of the mutant loci is essential for the formation of proper microtubule architecture in the axoneme of pronephric cilia. Mutants characterized in this study reveal intriguing genetic differences between subpopulations of embryonic cilia, and provide an opportunity to study several aspects of cilia structure and function.