Drosophila Apc2 Is a Cytoskeletally-Associated Protein That Regulates Wingless Signaling in the Embryonic Epidermis

The tumor suppressor adenomatous polyposis coli (APC) negatively regulates Wingless (Wg)/Wnt signal transduction by helping target the Wnt effector β-catenin or its Drosophila homologue Armadillo (Arm) for destruction. In cultured mammalian cells, APC localizes to the cell cortex near the ends of microtubules. Drosophila APC (dAPC) negatively regulates Arm signaling, but only in a limited set of tissues. We describe a second fly APC, dAPC2, which binds Arm and is expressed in a broad spectrum of tissues. dAPC2's subcellular localization revealed colocalization with actin in many but not all cellular contexts, and also suggested a possible interaction with astral microtubules. For example, dAPC2 has a striking asymmetric distribution in neuroblasts, and dAPC2 colocalizes with assembling actin filaments at the base of developing larval denticles. We identified a dAPC2 mutation, revealing that dAPC2 is a negative regulator of Wg signaling in the embryonic epidermis. This allele acts genetically downstream of wg, and upstream of arm, dTCF, and, surprisingly, dishevelled. We discuss the implications of our results for Wg signaling, and suggest a role for dAPC2 as a mediator of Wg effects on the cytoskeleton. We also speculate on more general roles that APCs may play in cytoskeletal dynamics

Insulin Signaling Mediates Sexual Attractiveness in Drosophila

Sexually attractive characteristics are often thought to reflect an individual's condition or reproductive potential, but the underlying molecular mechanisms through which they do so are generally unknown. Insulin/insulin-like growth factor signaling (IIS) is known to modulate aging, reproduction, and stress resistance in several species and to contribute to variability of these traits in natural populations. Here we show that IIS determines sexual attractiveness in Drosophila through transcriptional regulation of genes involved in the production of cuticular hydrocarbons (CHC), many of which function as pheromones. Using traditional gas chromatography/mass spectrometry (GC/MS) together with newly introduced laser desorption/ionization orthogonal time-of-flight mass spectrometry (LDI-MS) we establish that CHC profiles are significantly affected by genetic manipulations that target IIS. Manipulations that reduce IIS also reduce attractiveness, while females with increased IIS are significantly more attractive than wild-type animals. IIS effects on attractiveness are mediated by changes in CHC profiles. Insulin signaling influences CHC through pathways that are likely independent of dFOXO and that may involve the nutrient-sensing Target of Rapamycin (TOR) pathway. These results suggest that the activity of conserved molecular regulators of longevity and reproductive output may manifest in different species as external characteristics that are perceived as honest indicators of fitness potential

Two highly polymorphic CA repeats in the Menkes gene (ATP7A)

Two highly polymorphic CA repeats have been identified in the Menkes gene ( ATP7A ). These repeats should be useful for prenatal diagnosis and carrier detection in families with Menkes disease and X-linked cutis laxa. The observed heterozygosity for these two repeats was 0.778 and 0.60 in Centre d'Etude du Polymorphisme Humaine (CEPH) families.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47641/1/439_2004_Article_BF00210423.pd

Exclusion of BMP6 as a candidate gene for cleidocranial dysplasia

Cleidocranial dysplasia (CCD) is an autosomal dominant, generalized skeletal dysplasia in humans that has been mapped to the short arm of chromosome 6. We report linkage of a CCD mutation to 6p21 in a large family and exclude the bone morphogenetic protein 6 gene (BMP6) as a candidate for the disease by cytogenetic localization and genetic recombination. CCD was linked with a maximal two-point LOD score of 7.22 with marker D6S452 at θ = 0. One relative with a recombination between D6S451 and D6S459 and another individual with a recombination between D6S465 and CCD places the mutation within a 7 cM region between D6S451 and D6S465 at 6p21. A phage P1 genomic clone spanning most of the BMP6 gene hybridized to chromosome 6 in band region p23–p24 using FISH analysis, placing this gene cytogenetically more distal than the region of linkage for CCD. We derived a new polymorphic marker from this same P1 clone and found recombinations between the marker and CCD in this family. The results confirm the map position of CCD on 6p21, further refine the CCD genetic interval by identifying a recombination between D6S451 and D6S459, and exclude BMP6 as a candidate gene. Am. J. Med. Genet. 71:292–297, 1997. © 1997 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38269/1/9_ftp.pd

Safety and efficacy of l-tryptophan produced by fermentation with Escherichia coli KCCM 80152 for all animal species

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on l-tryptophan produced by fermentation using Escherichia coli KCCM 80152 when used as nutritional additive in feed and water for drinking for all animal species. The production strain and its recombinant DNA were not detected in the additive. l-Tryptophan, manufactured by fermentation with E. coli KCCM 80152, does not give rise to any safety concern with regard to the genetic modification of the production strain. The use of l-tryptophan produced using E. coli KCCM 80152 in supplementing feed to compensate for tryptophan deficiency in feedingstuffs is safe for non-ruminant target species. Using unprotected forms of tryptophan in ruminants can be a risk. The use of l-tryptophan produced by fermentation using E. coli KCCM 80152 in animal feed presents no concerns to consumers of animal products. Due to the content of endotoxins, the additive poses a risk for persons handling the additive when exposed by inhalation. The additive is not considered irritant for skin or eyes and is not considered a skin sensitiser. The additive under assessment is safe for the environment. The additive under assessment is regarded as an effective source of the amino acid l-tryptophan for all non-ruminant species. If l-tryptophan is intended for use in ruminants, it should be protected from ruminal degradation

Assessment of the application for renewal of authorisation of PHYZYME® XP 5000 G/L (6-phytase) for chickens for fattening, laying hens, turkeys for fattening, ducks for fattening, weaned piglets, pigs for fattening and sows for reproduction

PHYZYME\uae XP 5000 G/L is a feed additive that contains 6-phytase produced by a genetically modified strain of Schizosaccharomyces pombe. The applicant requested for the renewal of the authorisation for PHYZYME\uae XP 5000 G and L to be used as a feed additive in chickens for fattening, laying hens, turkeys for fattening, ducks for fattening, piglets (weaned), pigs for fattening and sows. This scientific opinion concerns the renewal of the authorisation of the additive for those species. To support the request, the applicant provided evidence that the additive in the market complies with the conditions of the authorisation. According to the information provided by the applicant, no new evidence has been identified that would make the FEEDAP Panel reconsider the previous conclusions regarding the safety for the target species, consumer, user and environment. The application for renewal of the authorisation did not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive. Therefore, there was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation

Safety and efficacy of the additive consisting of muramidase produced by Trichoderma reesei DSM 32338 (Balancius™) for use in weaned piglets (DSM Nutritional products Ltd)

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of muramidase produced by Trichoderma reesei DSM 32338 (Balancius™) as a feed additive for weaned piglets. The additive has been previously assessed by the FEEDAP Panel in the context of other applications, and in the current assessment the applicant requests for an extension of use. Based on the data available in a sub-chronic oral toxicity study, the Panel concluded that the additive is safe for weaned piglets at the maximum recommended level of 65,000 LSU(F)/kg feed. The additive is safe for the consumers and the environment but should be considered a potential respiratory sensitiser. The Panel could not conclude on the potential of the additive for skin/eye irritancy and skin sensitisation. The additive has the potential to be efficacious as a zootechnical additive for weaned piglets at the dose of 50,000 LSU(F)/kg feed

Safety and efficacy of l-tryptophan produced by fermentation with Escherichia coli KCCM 80135 for all animal species

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on l-tryptophan produced by fermentation using Escherichia coli KCCM 80135 when used as a nutritional additive in feed and water for drinking for all animal species. The production strain and its recombinant DNA were not detected in the additive. l-Tryptophan produced by fermentation with E. coli KCCM 80135 does not raise any safety concern with regard to the genetic modification of the production strain. The use of l-tryptophan produced using E. coli KCCM 80135 in supplementing feed to compensate for tryptophan deficiency in feedingstuffs is safe for non-ruminant target species. Using unprotected forms of tryptophan in ruminants can be a risk. The use of l-tryptophan produced by fermentation using E. coli KCCM 80135 in animal nutrition presents no safety concerns to consumers of animal products. l-Tryptophan produced by E. coli KCCM 80135 is not toxic by inhalation. The additive is not an irritant to skin and eyes, and it is not a skin sensitiser. The additive under assessment is considered safe for the environment. It is regarded as an effective source of the amino acid l-tryptophan for all non-ruminant species. If the additive l-tryptophan is intended for use in ruminants, it should be protected from ruminal degradation

Assessment of the application for renewal of the authorisation of Natuphos (3-phytase) as a feed additive for poultry and pigs

Natuphos \uae is a feed additive that contains 3-phytase which is produced \u25a0\u25a0\u25a0\u25a0\u25a0 The product is currently authorised for use as a feed additive in chickens for fattening, piglets (weaned) and pigs for fattening, laying hens and turkeys for fattening, ducks, sows, all minor avian species other than ducks and ornamental birds. This scientific opinion concerns the renewal of the authorisation of this additive for those species. The application also included chickens reared for laying/breeding, turkeys reared for breeding and breeding hens. The applicant provided evidence that the additive in the market complies with the conditions of authorisation. According to the information provided by the applicant, no new evidence has been identified that would make the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) reconsider the previous conclusions regarding the safety for the target species, consumer and environment under the authorised conditions of use. The additive is a respiratory sensitiser and a potential skin sensitiser. The present application for renewal of the authorisation does not include a proposal for amending or supplementing the conditions of the original authorisation that would have an impact on the efficacy of the additive. Therefore, there was no need for assessing the efficacy of the additive in for those species for which an authorisation exists. The Panel also considered that the additive is safe and has a potential to be efficacious in chickens reared for laying/breeding, turkeys reared for breeding, breeding hens and suckling piglets at the corresponding recommended doses

Safety and efficacy of l-leucine produced by fermentation with Escherichia coli NITE BP-02351 for all animal species

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on l-leucine produced by fermentation with Escherichia coli NITE BP-02351 when used as nutritional additive or as feed flavouring compound in feed and water for drinking for all animal species. The product under assessment is l-leucine produced by fermentation with a genetically modified strain of E. coli (NITE BP-02351). The production strain and its recombinant DNA were not detected in the final products. l-Leucine, manufactured by fermentation with E. coli NITE BP-02351, does not give rise to any safety concern to the production strain. The use of l-leucine produced with E. coli NITE BP-02351 is safe for the target species when used to supplement the diet in appropriate amounts. It is safe at the proposed use level of 25 mg/kg when used as flavouring compound for all animal species. The use of l-leucine produced by fermentation with E. coli NITE BP-02351 in animal nutrition raises no safety concerns for consumers of animal products. The additive is not irritating to the skin or eyes and is not a skin sensitiser. There is a risk for persons handling the additive from the exposure to endotoxins by inhalation. The use of l-leucine produced by E. coli NITE BP-02351 as feed additive does not represent a risk to the environment. The additive l-leucine produced by E. coli NITE BP-02351 is regarded as an effective source of the amino acid l-leucine when used as nutritional additive. For the supplemental l-leucine to be as efficacious in ruminants as in non-ruminant species, it requires protection against degradation in the rumen. It is also considered efficacious as feed flavouring compound under the proposed conditions of use