Summary of the Standards, Options and Recommendations for the use of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDP-PET scanning) in oncology (2002)

GuidelinePractice GuidelineResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Costs of insensitive acetylcholinesterase insecticide resistance for the malaria vector Anopheles gambiae homozygous for the G119S mutation

<p>Abstract</p> <p>Background</p> <p>The G119S mutation responsible for insensitive acetylcholinesterase resistance to organophosphate and carbamate insecticides has recently been reported from natural populations of <it>Anopheles gambiae </it>in West Africa. These reports suggest there are costs of resistance associated with this mutation for <it>An. gambiae</it>, especially for homozygous individuals, and these costs could be influential in determining the frequency of carbamate resistance in these populations.</p> <p>Methods</p> <p>Life-history traits of the AcerKis and Kisumu strains of <it>An. gambiae </it>were compared following the manipulation of larval food availability in three separate experiments conducted in an insecticide-free laboratory environment. These two strains share the same genetic background, but differ in being homozygous for the presence or absence of the G119S mutation at the <it>ace-1 </it>locus, respectively.</p> <p>Results</p> <p>Pupae of the resistant strain were significantly more likely to die during pupation than those of the susceptible strain. Ages at pupation were significantly earlier for the resistant strain and their dry starved weights were significantly lighter; this difference in weight remained when the two strains were matched for ages at pupation.</p> <p>Conclusions</p> <p>The main cost of resistance found for <it>An. gambiae </it>mosquitoes homozygous for the G119S mutation was that they were significantly more likely to die during pupation than their susceptible counterparts, and they did so across a range of larval food conditions. Comparing the frequency of G119S in fourth instar larvae and adults emerging from the same populations would provide a way to test whether this cost of resistance is being expressed in natural populations of <it>An. gambiae </it>and influencing the dynamics of this resistance mutation.</p

Western European Populations of the Ichneumonid Wasp Hyposoter didymator Belong to a Single Taxon

Hyposoter didymator (Hymenoptera, Ichneumonidae) is a generalist solitary endoparasitoid of noctuid larvae. In the present work, we tested whether populations of H. didymator were divided in several genetically distinct taxa as described for many other generalist parasitoid species, and whether differences in H. didymator parasitism rates were explained by the insect host species and/or by the plant on which these hosts were feeding on. The genetic analysis of natural populations collected in different regions in France and Spain on seven different insect hosts and seven different host plants (775 individuals) showed that H. didymator populations belong to a unique single taxon. However, H. didymator seems to be somewhat specialized. Indeed, in the fields it more often parasitized Helicoverpa armigera compared to the other host species collected in the present work. Also, H. didymator parasitism rates in field conditions and semi-field experimental studies were dependent on the host plants on which H. armigera larvae are feeding. Still, H. didymator can occur occasionally on non-preferred noctuid species. One hypothesis explaining the ability of H. didymator to switch hosts in natura could be related to fluctuating densities of the preferred host over the year; this strategy would allow the parasitoid to avoid seasonal population collapses

Differential Expression of Salivary Proteins between Susceptible and Insecticide-Resistant Mosquitoes of Culex quinquefasciatus

Background: The Culex quinquefasciatus mosquito, a major pest and vector of filariasis and arboviruses in the tropics, has developed multiple resistance mechanisms to the main insecticide classes currently available in public health. Among them, the insensitive acetylcholinesterase (ace-1(R) allele) is widespread worldwide and confers cross-resistance to organophosphates and carbamates. Fortunately, in an insecticide-free environment, this mutation is associated with a severe genetic cost that can affect various life history traits. Salivary proteins are directly involved in human-vector contact during biting and therefore play a key role in pathogen transmission. Methods and Results: An original proteomic approach combining 2D-electrophoresis and mass spectrometry was adopted to compare the salivary expression profiles of two strains of C. quinquefasciatus with the same genetic background but carrying either the ace-1(R) resistance allele or not (wild type). Four salivary proteins were differentially expressed (> 2 fold, P < 0.05) in susceptible (SLAB) and resistant (SR) mosquito strains. Protein identification indicated that the D7 long form, a major salivary protein involved in blood feeding success, presented lower expression in the resistant strain than the susceptible strain. In contrast, three other proteins, including metabolic enzymes (endoplasmin, triosephosphate isomerase) were significantly over-expressed in the salivary gland of ace-1(R) resistant mosquitoes. A catalogue of 67 salivary proteins of C. quinquefasciatus sialotranscriptome was also identified and described. Conclusion: The "resistance"-dependent expression of salivary proteins in mosquitoes may have considerable impact on biting behaviour and hence on the capacity to transmit parasites/viruses to humans. The behaviour of susceptible and insecticide-resistant mosquitoes in the presence of vertebrate hosts and its impact on pathogen transmission urgently requires further investigation

The Relationship between Population Structure and Aluminum Tolerance in Cultivated Sorghum

Background: Acid soils comprise up to 50% of the world's arable lands and in these areas aluminum (Al) toxicity impairs root growth, strongly limiting crop yield. Food security is thereby compromised in many developing countries located in tropical and subtropical regions worldwide. In sorghum, SbMATE, an Al-activated citrate transporter, underlies the Alt(SB) locus on chromosome 3 and confers Al tolerance via Al-activated root citrate release. Methodology: Population structure was studied in 254 sorghum accessions representative of the diversity present in cultivated sorghums. Al tolerance was assessed as the degree of root growth inhibition in nutrient solution containing Al. A genetic analysis based on markers flanking Alt(SB) and SbMATE expression was undertaken to assess a possible role for Alt(SB) in Al tolerant accessions. In addition, the mode of gene action was estimated concerning the Al tolerance trait. Comparisons between models that include population structure were applied to assess the importance of each subpopulation to Al tolerance. Conclusion/Significance: Six subpopulations were revealed featuring specific racial and geographic origins. Al tolerance was found to be rather rare and present primarily in guinea and to lesser extent in caudatum subpopulations. Alt(SB) was found to play a role in Al tolerance in most of the Al tolerant accessions. A striking variation was observed in the mode of gene action for the Al tolerance trait, which ranged from almost complete recessivity to near complete dominance, with a higher frequency of partially recessive sources of Al tolerance. A possible interpretation of our results concerning the origin and evolution of Al tolerance in cultivated sorghum is discussed. This study demonstrates the importance of deeply exploring the crop diversity reservoir both for a comprehensive view of the dynamics underlying the distribution and function of Al tolerance genes and to design efficient molecular breeding strategies aimed at enhancing Al tolerance.CGIAR[G3007.04]McKnight FoundationFundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG)National Council for Scientific and Technological Development (CNPq

Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid–Activated Receptor

The chicken ovalbumin upstream promoter-transcription factors (COUP-TFI and II) make up the most conserved subfamily of nuclear receptors that play key roles in angiogenesis, neuronal development, organogenesis, cell fate determination, and metabolic homeostasis. Although the biological functions of COUP-TFs have been studied extensively, little is known of their structural features or aspects of ligand regulation. Here we report the ligand-free 1.48 Å crystal structure of the human COUP-TFII ligand-binding domain. The structure reveals an autorepressed conformation of the receptor, where helix α10 is bent into the ligand-binding pocket and the activation function-2 helix is folded into the cofactor binding site, thus preventing the recruitment of coactivators. In contrast, in multiple cell lines, COUP-TFII exhibits constitutive transcriptional activity, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, and ligand binding, substantially reduce the COUP-TFII transcriptional activity. Importantly, retinoid acids are able to promote COUP-TFII to recruit coactivators and activate a COUP-TF reporter construct. Although the concentration needed is higher than the physiological levels of retinoic acids, these findings demonstrate that COUP-TFII is a ligand-regulated nuclear receptor, in which ligands activate the receptor by releasing it from the autorepressed conformation

Evidence of Introgression of the ace-1R Mutation and of the ace-1 Duplication in West African Anopheles gambiae s. s

Background: The role of inter-specific hybridisation is of particular importance in mosquito disease vectors for predicting the evolution of insecticide resistance. Two molecular forms of Anopheles gambiae s.s., currently recognized as S and M taxa, are considered to be incipient sibling species. Hybrid scarcity in the field was suggested that differentiation of M and S taxa is maintained by limited or absent gene flow. However, recent studies have revealed shared polymorphisms within the M and S forms, and a better understanding of the occurrence of gene flow is needed. One such shared polymorphism is the G119S mutation in the ace-1 gene (which is responsible for insecticide resistance); this mutation has been described in both the M and S forms of A. gambiae s.s. Methods and Results: To establish whether the G119S mutation has arisen independently in each form or by genetic introgression, we analysed coding and non-coding sequences of ace-1 alleles in M and S mosquitoes from representative field populations. Our data revealed many polymorphic sites shared by S and M forms, but no diversity was associated with the G119S mutation. These results indicate that the G119S mutation was a unique event and that genetic introgression explains the observed distribution of the G119S mutation within the two forms. However, it was impossible to determine from our data whether the mutation occurred first in the S form or in the M form. Unexpectedly, sequence analysis of some resistant individuals revealed a duplication of the ace-1 gene that was observed in both A. gambiae s.s. M and S forms. Again, the distribution of this duplication in the two forms most likely occurred through introgression. Conclusions: These results highlight the need for more research to understand the forces driving the evolution of insecticide resistance in malaria vectors and to regularly monitor resistance in mosquito populations of Africa

Hereditary cataract in the Bengal cat in Poland

Background: This paper reports the significant prevalence of a presumed hereditary cataract in the Bengal cat breed in Poland. The nuclear part of the lens is affected and previous reports from Sweden and France for this type of feline cataract suggest that a recessive mode of inheritance is probably involved. Results: Presumed congenital or neonatal cataract involving the posterior nuclear part of each lens was initially diagnosed in a 12 month old male Bengal cat. As both parents and a sibling were also affected with cataract, a group of 18 related and 11 non-related cats was then subsequently examined. Eight related cats and one non- related cat were found to be similarly affected. A breed survey was then completed using an additional five centres across Poland and a further 190 related cats were examined. A total of 223 cats have been involved in this study, with 75 (33%) being affected with several types of cataract and 67 (30%) being specifically affected with the same or similar nuclear lesions. Eight cats (3.6%) presented with other cataract types and a prominence of the posterior lens suture lines was recorded in 65 cats unaffected with cataract (29%). There were no demonstrable vision problems. Neither age nor coat colour was significantly associated with the nuclear cataract, but the nuclear cataract group had a higher proportion of females than the unaffected group. Pedigree analysis has indicated probable inheritance as a recessive trait. Conclusions: These findings suggest that a presumably inherited nuclear cataract is present in the Bengal cat breed in Poland. It is considered to be either congenital or of very early onset, probably being inherited as a recessive trait. Although the lesion has no noticeable effect on vision, breeders in Poland and worldwide should be aware of the disease and clinical examination of young breeding stock prior to reproduction is advisable

Estrogen receptor transcription and transactivation: Structure-function relationship in DNA- and ligand-binding domains of estrogen receptors

Estrogen receptors are members of the nuclear receptor steroid family that exhibit specific structural features, ligand-binding domain sequence identity and dimeric interactions, that single them out. The crystal structures of their DNA-binding domains give some insight into how nuclear receptors discriminate between DNA response elements. The various ligand-binding domain crystal structures of the two known estrogen receptor isotypes (α and β) allow one to interpret ligand specificity and reveal the interactions responsible for stabilizing the activation helix H12 in the agonist and antagonist positions

Molecular Evolution of Ultraspiracle Protein (USP/RXR) in Insects

Ultraspiracle protein/retinoid X receptor (USP/RXR) is a nuclear receptor and transcription factor which is an essential component of a heterodimeric receptor complex with the ecdysone receptor (EcR). In insects this complex binds ecdysteroids and plays an important role in the regulation of growth, development, metamorphosis and reproduction. In some holometabolous insects, including Lepidoptera and Diptera, USP/RXR is thought to have experienced several important shifts in function. These include the acquisition of novel ligand-binding properties and an expanded dimerization interface with EcR. In light of these recent hypotheses, we implemented codon-based likelihood methods to investigate if the proposed shifts in function are reflected in changes in site-specific evolutionary rates across functional and structural motifs in insect USP/RXR sequences, and if there is any evidence for positive selection at functionally important sites. Our results reveal evidence of positive selection acting on sites within the loop connecting helices H1 and H3, the ligand-binding pocket, and the dimer interface in the holometabolous lineage leading to the Lepidoptera/Diptera/Trichoptera. Similar analyses conducted using EcR sequences did not indicate positive selection. However, analyses allowing for variation across sites demonstrated elevated non-synonymous/synonymous rate ratios (dN/dS), suggesting relaxed constraint, within the dimerization interface of both USP/RXR and EcR as well as within the coactivator binding groove and helix H12 of USP/RXR. Since the above methods are based on the assumption that dS is constant among sites, we also used more recent models which relax this assumption and obtained results consistent with traditional random-sites models. Overall our findings support the evolution of novel function in USP/RXR of more derived holometabolous insects, and are consistent with shifts in structure and function which may have increased USP/RXR reliance on EcR for cofactor recruitment. Moreover, these findings raise important questions regarding hypotheses which suggest the independent activation of USP/RXR by its own ligand