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Experimental evolution of a pathogen confronted with innate immune memory increases variation in virulence.

Understanding the drivers and mechanisms of virulence evolution is still a major goal of evolutionary biologists and epidemiologists. Theory predicts that the way virulence evolves depends on the balance between the benefits and costs it provides to pathogen fitness. Additionally, host responses to infections, such as resistance or tolerance, play a critical role in shaping virulence evolution. But, while the evolution of pathogens has been traditionally studied under the selection pressure of host adaptive immunity, less is known about their evolution when confronted to simpler and less effective forms of immunity such as immune priming. In this study, we used a well-established insect model for immune priming - red flour beetles and their bacterial pathogen Bacillus thuringiensis tenebrionis - to test how this form of innate immune memory drives the pathogen evolution. Through controlled experimental evolution of the pathogen in primed versus non-primed hosts, we found no change in average virulence after eight selection cycles in primed host. Nonetheless, we observed a notable rise in the variability of virulence, defined as the ability to kill hosts, among independent pathogen lines that evolved in primed hosts, and the bacteria were unable to develop resistance to host priming. Whole genome sequencing revealed increased activity in the bacterial mobilome (prophages and plasmids). Expression of the Cry toxin - a well-known virulence factor - was linked to evolved differences in copy number variation of the cry-carrying plasmid, though this did not correlate directly with virulence. These findings highlight that innate immune memory can drive variability in pathogen traits, which may favor adaptation to variable environments. This underscores the need to consider pathogen evolution in response to innate immune memory when applying these mechanisms in medicine, aquaculture, pest control, and insect mass production.

Animals↗

Quantitative detection of the potato cyst nematode, Globodera pallida, and the beet cyst nematode, Heterodera schachtii, using Real-Time PCR with SYBR green I dye.

The potato cyst nematode Globodera pallida and the beet cyst nematode Heterodera schachtii are major nematode pests in world agriculture. Precise identification and knowledge about the number of nematodes in field soil are necessary to develop effective integrated pest control. Here we report the results of the Real-Time PCR assay for the rapid detection and quantification of G. pallida and H. schachtii. Using species specific primers and SYBR green I dye, we were able to detect a single second stage juvenile of cyst forming nematodes in samples. The specificity of the reaction was confirmed by the lack of amplification of DNAs from other Heterodera or Globodera species. Validation tests showed a rather high correlation between real numbers of second stage juveniles in a sample and expected numbers detected by Real-Time PCR. Reasons for observed differences in sensitivity and reliability of quantification detection for two species as well as other problems of Real-Time PCR are discussed. The Real-Time PCR assay with SYBR green I dye targeting fragments of the ITS-rDNA provided a sensitive means for the rapid and simultaneous detection and quantification of juveniles of these pests.

Animals↗

The chemistry of defense: theory and practice.

Defensive chemicals used by organisms for protection against potential consumers are generally products of secondary metabolism. Such chemicals are characteristic of free-living organisms with a limited range of movement or limited control over their movements. Despite the fact that chemical defense is widespread among animals as well as plants, the vast majority of theories advanced to account for patterns of allocation of energy and materials to defensive chemistry derive exclusively from studies of plant-herbivore interactions. Many such theories place an undue emphasis on primary physiological processes that are unique to plants (e.g., photosynthesis), rendering such theories limited in their utility or predictive power. The general failure of any single all-encompassing theory to gain acceptance to date may indicate that such a theory might not be a biologically realistic expectation. In lieu of refining theory, focusing attention on the genetic and biochemical mechanisms that underlie chemical defense allocation is likely to provide greater insights into understanding patterns across taxa. In particular, generalizations derived from understanding such mechanisms in natural systems have immediate applications in altering patterns of human use of natural and synthetic chemicals for pest control.

Animals↗

Evidence of anopheline mosquito resistance to agrochemicals in northern Thailand.

The objective of this study was to assess insecticide resistance in anopheline mosquito populations in agroecosystems with high and low insecticide use in a malaria endemic area in Chiang Mai province in northern Thailand. Anopheline mosquitoes were collected in May and June 2004 from two locations with different agricultural insecticide intensity (HIGH and LOW), but similar in vector control strategies. The F1-generation of Anopheles maculatus s.s. and An. sawadwongporni were subjected to diagnostic doses of methyl parathion (MeP) and cypermethrin (Cyp), both commonly used insecticides in fruit orchards in Thailand. An. minimus A from the HIGH location was subjected to diagnostic doses to Cyp. CDC bottle bioassays were used to determine insecticide susceptibility. Time-mortality data were subjected to Probit analyses to estimate lethal time values (LT50 and LT90). Lethal time ratios (LTR) were computed to determine differences in lethal time response between populations from HIGH and LOW locations. The mortality of An. maculatus to MeP was 74% and 92% in the HIGH and LOW locations, respectively. The corresponding figures for An. sawadwongporni were 94% and 99%. There was no indication of resistance to Cyp for all species tested in either location. The LT90 and LT50 values of An. maculatus s.s. subjected to diagnostic doses of MeP were significantly different between locations (p<0.05). Reduced susceptibility to MeP in mosquito populations in the HIGH location is caused by intensive agricultural pest control and not by vector control activities, because organophosphates have never been used for vector control in the area. Our results indicate that there are still susceptible anopheline populations to pyrethroids, which is consistent with other research from the region. Therefore, there is presently no direct threat to vector control. However increased use of pyrethroids in agriculture may cause problems for future vector control.

Agrochemicals↗

Time course variations of antioxidant enzyme activities and histopathology of gilthead seabream gills exposed to malathion.

In a widely distributed and commercially important fish, gilthead seabream Sparus aurata L., we have studied sublethal effects of malathion in order to identify early warning bioindicators of exposure before irreversible damage occurs. To achieve this goal, groups of 10 juvenile specimens were exposed for 24, 48, 72 and 96 h to a sublethal concentration of malathion (0.4 mg/l). Another group was used as control. The activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) and histopathological features from exposed gills were assessed. It should also be mentioned that no mortality was observed during the whole experience. The activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were altered significantly from 24 h onward (p<0.05). It is of interest to note that catalase activity was decreased after exposure instead of increasing as other antioxidant enzymes assessed. On the other hand, histopathological alterations of the gills were observed as early as at 48 h-exposure, but the most severe damage occurred at 96 h exposure. The evidence presented here, together with other data from the literature, unequivocally established oxidative-stress-inducing effects of malathion in gilthead seabream Sparus aurata. It is also concluded antioxidants employed (SOD, CAT and GPX) changed significantly a long time before histopathological alterations of gills became evident. Consequently, these antioxidant enzymes may be highly recommended as early-warning bioindicators of environmental pollution by malathion in the areas where it is proposed to be used in pest control activities.

Animals↗

Prevalence of Salmonella organisms in swine feed.

OBJECTIVE: To test feed and feed ingredients on swine farms for Salmonella organisms and to analyze data from these farms to determine risk factors associated with Salmonella organisms in the feed and feed ingredients. DESIGN: Epidemiologic survey and retrospective case-control study. SAMPLE POPULATION: 30 swine farms. PROCEDURE: Samples of feed and feed ingredients and information regarding herd characteristics were collected from 30 swine farms. Samples were tested for Salmonella organisms, and data compiled from herd information forms were examined for associated risk factors between herd characteristics and isolation of Salmonella organisms. RESULTS: Salmonella organisms were isolated from 36 of 1,264 (2.8%) feed and feed ingredient samples and from 14 of 30 (46.7%) farms. Thirteen Salmonella sp serotypes and 2 untypeable isolates were cultured. Recovery of Salmonella organisms from at least 1 feed or feed ingredient on a farm was significantly associated with 6 herd characteristics (lack of bird-proofing, using farm-prepared feed for finishing-age pigs rather than purchased feed, and housing pigs in facilities other than total confinement in the growing, finishing, gestating, and breeding stages of production, respectively). Isolation of Salmonella sp was not associated with a history of salmonellosis on a farm. CLINICAL IMPLICATIONS: Salmonella organisms were readily isolated from samples of feed and feed ingredients, illustrating that salmonellae are ubiquitous in a farm environment. Implementing sanitary and pest-control measures continues to be a prudent recommendation. Salmonella serotypes found in feed and feed ingredients have the potential to cause disease in pigs that consume the feed or, ultimately, in people that consume pork.

Animal Feed↗

Rabbit haemorrhagic disease: field epidemiology and the management of wild rabbit populations.

Rabbit haemorrhagic disease (RHD) has become established in wild rabbit populations throughout Western Europe, Australia and New Zealand. The abundance of wild rabbits has been significantly reduced, particularly in drier areas of southern Spain, inland Australia and South Island New Zealand. A detailed knowledge of the epidemiology of RHD is essential for the management of the disease in natural rabbit populations, either to rebuild or to control populations. When RHD first spread among naive wild rabbits, epidemiological studies provided unique information on the rate of spread, the possible role of insect vectors in transmission, and the correlation between the impact of disease on populations and climatic variables. Current research shows a consistent pattern of epidemiology between Europe and Australasia. Typically, the most severe epizootics of RHD occur among young sub-adult rabbits which have lost age-related resilience and maternal antibodies. However, the timing of these outbreaks reflects climatic variables that determine the breeding season of the rabbits and the periods when RHD virus (RDHV) is most likely to persist and spread. Further factors that may complicate epidemiology include the possibility that non-pathogenic RHDV-like viruses are present in natural rabbit populations. Additionally, the question of how the virus persists from year to year remains unresolved; persistence in carrier rabbits is a possibility. Understanding of the epidemiology of RHD is now sufficiently advanced to consider the possibility of manipulating rabbit populations to alter the epidemiological pattern of RHD and thereby maximise or minimise the mortality caused by the disease. Altering the epidemiology of RHD in this manner would assist the management of wild rabbit populations either for conservation or pest control purposes.

Animals↗

Increased transcription of CYP6D1 causes cytochrome P450-mediated insecticide resistance in house fly.

Insecticide resistance is a major problem that continues to plague efforts to control pests of animals and crops. An important mechanism by which insects become resistant to insecticides is via increased detoxification mediated by the cytochrome P450 microsomal monooxygenases (monooxygenases). One of the fundamental gaps in our knowledge about this resistance mechanism is an understanding of how insects express high levels of the specific cytochrome P450(s) responsible for resistance. One such P450, CYP6D1, causes resistance to pyrethroid in the house fly and is expressed at 9-fold higher levels (mRNA and protein) in the Learn Pyrethroid Resistant (LPR) strain (compared to susceptible strains). The relative stability of CYP6D1 mRNA in resistant and susceptible strains was measured following inhibition of transcription with actinomycin D. The same time course of decrease in CYP6D1 mRNA abundance was detected in both strains indicating that the high level of expression of CYP6D1 in LPR is not due to increased stability of the mRNA. The comparative rates of transcription of CYP6D1 were measured using an in vitro run-on transcription assay. The relative amount of CYP6D1 transcript produced in this assay was 10-fold greater in the LPR strain compared to the susceptible strain. This demonstrates that increased transcription of CYP6D1 is an underlying cause of monooxygenase-mediated insecticide resistance. The increased rate of transcription of CYP6D1 in the resistant strain (LPR) is controlled by two factors: one on autosome 1 and another on autosome 2.

Animals↗

Knowledge, attitudes and practices (KAP) among agricultural extension workers concerning the reduction of the adverse impact of pesticides in agricultural areas in Tanzania.

BACKGROUND: Extension workers are educated locally to enable them to train farmers in using improved local farming methods and imported technology, such as pesticides, to increase crop production. However, the extension workers are not adequately trained in health aspects of pesticides and hence are unable to provide adequate services to farmers with regard to safe use of pesticides. OBJECTIVE: The present study assessed the knowledge, attitudes and practices of agricultural extension workers with respect to health effects of pesticides in order to develop strategies for the control of pesticide exposure and prevention of pesticide poisoning in Tanzania. METHODS: A survey of Tanzanian agricultural extensionists was undertaken in 1991-1994 using a standardized questionnaire in face-to-face interviews. Extensionists who were district agricultural officers, assistant agricultural officers, agricultural assistants, and field assistants, working in the coffee and cotton growing areas (N = 61) within a radius of 15 km of farm, estate or village under farm worker study (reported elsewhere) were included in the survey. RESULTS: The majority of extensionists knew that pesticides could enter the human body but only a quarter perceived pesticides as a major problem in the community they served. The majority showed awareness of potential health hazards of the different pesticides used in their service areas, but they did not recognize what pesticides were responsible for poisoning. A high proportion was familiar with first aid procedures in case of pesticide poisoning; however, many procedures described were not appropriate for pesticide poisoning. CONCLUSIONS: The survey indicated that training of agricultural workers in health aspects of pesticide exposure is an important task for adequate provision of service to farmers with regard to safe use of pesticides in Tanzania. Nevertheless, the appropriate role of extensionists in reducing the health impact of pesticides would be to advocate pesticides of low toxicity or non-chemical pest control.

Adult↗

Reference values for metabolites of pyrethroid and organophosphorous insecticides in urine for human biomonitoring in environmental medicine.

Pesticides are widely used throughout the world in agriculture to protect crops, and in public health to control diseases transmitted by vectors or intermediate hosts. After the prohibition of organochlorines, such as DDT, today mainly pyrethroids and organophosphorous insecticides are used. With reliable and sensitive analytical methods for detecting metabolites of organophosphorous and pyrethroid insecticides in urinary specimens of the general population several studies have been published on internal exposure to these insecticides of the population in Germany. In total, data on levels of metabolites of organophosphorous acids in urine of about 1200 children and adults have been published, as well as data on levels of pyrethroid metabolites in urine of about 2100 children and adults. In Germany, reference values for environmental pollutants related to the population are established continuously by the Human Biomonitoring Commission of the German Federal Environmental Agency, preferably based on data gained by representative studies. Reference values are defined as the 95th percentile, rounded off within the 95% confidence interval of the population studied. Since there is a need for reference values to characterise the population's exposure to organophosphates and pyrethroids, and since there are different studies available from Germany that agree quite well with data from other industrialised countries, the Commission has derived reference values from the available data, though none of the studies had fulfilled criteria on representativity. Reference values for metabolites of organophosphorous acids are as follows: DMP 135 microg/l, DMTP 160 microg/l and DEP 16 microg/l and for metabolites of pyrethroids: cis-Cl2CA 1 microg/l, trans-Cl2CA 2 microg/l and 3-PBA 2 microg/l. As the volume-related concentrations of organophosphate and pyrethroid metabolites show no significant age-dependence, the reference values derived are not age-stratified. Though based merely on statistical and not on toxicological data, levels analysed above the reference levels, when reliably measured (verified several times), should prompt environmental health practitioners to search for sources, within the bounds of proportionality. In addition to accidental poisoning, possible sources include indoor contamination following improper pest control operations in homes as well as in pets and food products contaminated by these pesticides.

Adolescent↗

Genotoxicity of select herbicides in Rana catesbeiana tadpoles using the alkaline single-cell gel DNA electrophoresis (comet) assay.

Pesticides are broadly used for pest control in agriculture despite possible negative impacts they may pose to the environment. Thus, we examined the DNA damage caused by five herbicides commonly used in southern Ontario (Canada). Erythrocytes from Rana catesbeiana (bullfrog) tadpoles were evaluated for DNA damage following exposure to selected herbicides, using the alkaline single-cell gel DNA electrophoresis (SCG) or "comet" assay [Singh et al. (1988): Exp Cell Res 175:184-191; Ralph et al. (1996): Eviron Mol Mutagen 28:112-120]. This approach involves detection, under alkaline conditions, of DNA fragments that upon electrophoresis migrate from the nuclear care, resulting in a comet formation. The herbicides tested, along with their active ingredients, were AAtrex Nine-O (atrazine), Dual-960E (metalochlor), Roundup (glyphosate), Sencor-500F (metribuzin), and Amsol (2,4-D amine). Tadpoles were exposed in the laboratory for a 24-hr period to several concentrations of the herbicides dissolved in dechlorinated water. Methyl methanesulphonate was used as a positive control. The herbicides AAtrex Nine-O-, Dual-960E-, Roundup-, and Sencor-500F-treated tadpoles showed significant DNA damage when compared with unexposed control animals, whereas, Amsol-treated tadpoles did not. Unlike the other responding herbicides, Sencor-500F did not show a relationship between dosage and DNA damage. In summary, the results indicate that at least some of the herbicides currently used in southern Ontario are capable of inducing DNA damage in tadpoles.

Animals↗

Sequence and analysis of zona pellucida 2 cDNA (ZP2) from a marsupial, the brushtail possum, Trichosurus vulpecula.

All mammalian eggs are surrounded by the zona pellucida, an extracellular coat involved in vital functions during fertilization and early development. The zona pellucida glycoproteins are promising antigenic targets for development of contraceptive vaccines to control pest populations of marsupials in Australia and New Zealand. Our current understanding of the function of the zona pellucida glycoproteins is based almost entirely on the mouse and may not be representative of gamete interactions in all eutherian or marsupial mammals. This study reports the isolation and characterization of the ZP2 gene from the brushtail possum (Trichosurus vulpecula). The brushtail possum ZP2 mRNA is 2,182 nucleotides long with an open reading frame coding for a polypeptide chain of 712 amino acids with a molecular mass of 79,542 d. The deduced amino acid sequence of possum ZP2 is 48 to 55% identical to that of eutherian mammals. It shares several structural characteristics including N-linked glycosylation sites, location and number of cysteine residues, and hydropathy profile. The brushtail possum ZP2 gene is expressed exclusively in the ovary. Further studies are planned to elucidate the specific site of ZP2 expression within the ovary and its function during fertilization in marsupials.

Amino Acid Sequence↗

Occurrence of ion transport peptide (ITP) and ion transport-like peptide (ITP-L) in orthopteroids.

Comparison of the sequence and biological activity of ITP-related proteins from other insects on Schistocerca hindgut will provide further understanding of ITP interaction with its receptor (ITPR) and may thus open new avenues of insect pest control if good ITPR antagonists can be developed. Using a specific bioassay (measurement of ileal Cl- transport) and Western blot analysis with antibodies raised to Schistocerca ion transport peptide (ScgITP) sequences, we demonstrate stimulatory ITP-related peptides in the corpora cardiaca (CC) of several othopteran insects (Schistocerca gregaria, Locusta migratoria, Melanoplus sanguinipes, Xanthippus corallipes, Carausius morosus, Periplaneta americana and Acheta domesticus.). For the first time, we have immunologically detected ITP in Schistocerca brain, the tissue in which ITP transcripts are found and which has some activity in the bioassay. Neither reciprocal bioassays nor immunological results reveal any differences between two locust species, Locusta and Schistocerca, which is consistent with cDNA analysis. Using Schistocerca-derived primers and the polymerase chain reaction (PCR), we show that Locusta brain contains RNA encoding for peptides with identical sequence to ScgITP and with only a single neutral amino acid change from Schistocerca ion transport-like peptide (ScgITP-L). We present evidence that ITP-L transcripts are present in at least 3 locust/grasshopper genera but have been unable to detect ITP-L peptide to date in any tissues assayed by Western blotting at a detection limit of 0.8 pmol/tissue. Results indicate high conservation of ITP structure and biological activity among these orthopteroids, in contrast to several other insect orders.

Amino Acid Sequence↗

The repellant and antifeedant properties of Cyperus articulatus against Tribolium casteneum Hbst.

Cyperus articulatus is an insect repellant plant commonly found in Northern Nigeria and used traditionally in pest control. The light petroleum and methanol extracts of the plant's rhizome were evaluated against Tribolium casteneum Hbst (the red flour beetle) using standard techniques. The methanol extract showed more antifeedant property than the light petroleum extract, while both the extracts were observed to have similar repellant actions.

Animals↗

Insecticide action at the GABA-gated chloride channel: recognition, progress, and prospects.

Three billion (3 x 10(9)) pounds of hexachlorocyclohexanes, polychlorobornanes, and chlorinated cyclodienes (such as lindane, toxaphene, and endosulfan, respectively) were used to control pest insects before their mode of action was established as blocking the GABA-gated chloride channel. With the restricted use or demise of these polychlorocycloalkanes (each approximately 50 to approximately 75% by weight of chlorine), the GABAergic system is for now an underutilized target of insecticide action. Newer compounds with outstanding potency at this receptor and as toxicants to houseflies are suitably-substituted 2,6,7-trioxabicyclo[2.2.2]-octanes, particularly the bicycloorthobenzoates, and 1,3-dithianes, including those with no halogenated substituents. Picrotoxinin analogs and alkynylphenyl-silatranes also act at this target but are of lower insecticidal activity. [3H]n-Propyl-ethynylbicycloorthobenzoate ([3H]EBOB) is for now the best radioligand for this insecticidally-relevant binding site in insects. Macrocyclic lactones such as the avermectins and moxidectin act at a different binding site to disrupt chloride flux and they have a different spectrum of insecticidal activity and no cross resistance with cyclodienes in houseflies. The search for new insecticides has provided the incentive and probes for a better understanding of the insect GABAergic system.

Animals↗

Prospects of using Drosophila for insect neuroendocrine research.

Classical and in vitro approaches for the analysis of the molecular components of neuroendocrine systems often disrupt their close interaction with other bodily systems, which is a crucial aspect of their function in vivo. "Genetic dissection" is an alternative, noninvasive approach which involves the systematic generation of mutations in individual genes, followed by in vivo analysis of the phenotypic effects of altering a single protein at a time avoiding extraneous disruptions. Among insects Drosophila melanogaster is the most suitable model for this approach. This paper explores the application of genetic and molecular techniques available in Drosophila for studying its neuroendocrine system with special emphasis on the production of ecdysone and juvenile hormone. Strategies are described for the generation and identification of endocrine mutations, especially those affecting hormone synthesis and regulation. Once identified by a specific mutation, a gene in Drosophila can be cloned either by chromosomal microdissection and "chromosomal walk" or by transposon tagging. Methods for molecular analysis of the structure and function of a cloned gene and of the protein it encodes are available for further study. Alternatively, a gene can be cloned using heterologous DNA probes or oligonucleotides designed according to the amino acid sequence of a protein. Genes may also be cloned via their pattern of expression (using stage- or tissue-specific cDNA libraries or through transposon-mediated "enhancer detection." Anti-sense RNA, the replacement of the gene by in vitro manipulated versions, or mutagenesis of its endogenous copies can then be used for studying its function in vivo. Information about endocrine genes in Drosophila as well as material such as cloned genes and antibodies should be useful for the analysis of endocrine systems in other insects which are not amenable to genetic manipulations. Such information should be helpful in designing novel means for pest control based on the specific intervention with endocrine systems regulating insect development and reproduction.

Animals↗

Bioengineering nitrogen acquisition in rice: can novel initiatives in rice genomics and physiology contribute to global food security?

Rice is the most important crop species on earth, providing staple food for 70% of the world's human population. Over the past four decades, successes in classical breeding, fertilization, pest control, irrigation and expansion of arable land have massively increased global rice production, enabling crop scientists and farmers to stave off anticipated famines. If current projections for human population growth are correct, however, present rice yields will be insufficient within a few years. Rice yields will have to increase by an estimated 60% in the next 30 years, or global food security will be in danger. The classical methods of previous green revolutions alone will probably not be able to meet this challenge, without being coupled to recombinant DNA technology. Here, we focus on the promise of these modern technologies in the area of nitrogen acquisition in rice, recognizing that nitrogen deficiency compromises the realization of rice yield potential in the field more than any other single factor. We summarize rice-specific advances in four key areas of research: (1). nitrogen fixation, (2). primary nitrogen acquisition, (3). manipulations of internal nitrogen metabolism, and (4). interactions between nitrogen and photosynthesis. We develop a model for future plant breeding possibilities, pointing out the importance of coming to terms with the complex interactions among the physiological components under manipulation, in the context of ensuring proper targeting of intellectual and financial resources in this crucial area of research.

Biotechnology↗

Edit, cut and paste in the nicotinic acetylcholine receptor gene family of Drosophila melanogaster.

Nicotinic acetylcholine receptors (nAChRs) are important for fast synaptic cholinergic transmission. They are targets of drugs/chemicals for human and animal health as well as for pest control. With the advent of genome sequencing, entire nAChR gene families have now been described for vertebrates and invertebrates. Mostly, these are extensive with a large number of distinct subunits, making possible many nAChR subtypes differing in transmitter affinity, channel conductance, ion selectivity, desensitization, modulation and pharmacology. The smallest nAChR gene family to date is that of the fruit fly, Drosophila melanogaster, with only 10 members. This apparently compact family belies its true diversity as 4 of the 10 subunits show alternative splicing. Also, using Drosophila, A-to-I pre-mRNA editing has been demonstrated for the first time in nAChRs. Such is the extent of this variation, that one subunit alone (Dalpha6) can potentially generate far more isoforms than seen in entire gene families from other species. We present here three-dimensional models constructed for insect nAChRs, which show that many variations introduced by alternative splicing and RNA editing may influence receptor function.

Alternative Splicing↗