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PubMed2005

Analysis of RUNX1 binding site and RAPTOR polymorphisms in psoriasis: no evidence for association despite adequate power and evidence for linkage.

BACKGROUND: A previous study identified two peaks of allelic association between psoriasis and single nucleotide polymorphisms (SNPs) mapping to distal chromosome 17q, including a disease associated SNP that leads to loss of a RUNX1 transcription factor binding site, and additional SNPs in the third intron of the RAPTOR gene. Another study found an association with SNPs in the RAPTOR gene, but not with the RUNX1 binding site polymorphism. METHODS: In an effort to confirm these observations, we genotyped 579 pedigrees containing 1285 affected individuals for three SNPs immediately flanking and including the RUNX1 binding site, and for three SNPs in the RAPTOR gene. RESULTS: Here we report further evidence for linkage to distal chromosome 17q, with a linkage peak mapping 1.7 cM distal to the RUNX1 binding site (logarithm of the odds 2.26 to 2.73, depending upon statistic used). However, we found no evidence for association to individual SNPs or haplotypes in either of the previously identified peaks of association. Power analysis demonstrated 80% power to detect significant association at genotype relative risks of 1.2 (additive and multiplicative models) to 1.5 (dominant and recessive models) for the RUNX1 binding site, and 1.3 to 1.4 for the RAPTOR locus under all models except dominant. CONCLUSIONS: Our data provide no support for the previously identified RUNX1 binding site or for the RAPTOR locus as genetic determinants of psoriasis, despite evidence for linkage of psoriasis to distal chromosome 17q.

Adaptor Proteins, Signal Transducing↗
PubMed2003

RAPTOR: optimal protein threading by linear programming.

This paper presents a novel linear programming approach to do protein 3-dimensional (3D) structure prediction via threading. Based on the contact map graph of the protein 3D structure template, the protein threading problem is formulated as a large scale integer programming (IP) problem. The IP formulation is then relaxed to a linear programming (LP) problem, and then solved by the canonical branch-and-bound method. The final solution is globally optimal with respect to energy functions. In particular, our energy function includes pairwise interaction preferences and allowing variable gaps which are two key factors in making the protein threading problem NP-hard. A surprising result is that, most of the time, the relaxed linear programs generate integral solutions directly. Our algorithm has been implemented as a software package RAPTOR-RApid Protein Threading by Operation Research technique. Large scale benchmark test for fold recognition shows that RAPTOR significantly outperforms other programs at the fold similarity level. The CAFASP3 evaluation, a blind and public test by the protein structure prediction community, ranks RAPTOR as top 1, among individual prediction servers, in terms of the recognition capability and alignment accuracy for Fold Recognition (FR) family targets. RAPTOR also performs very well in recognizing the hard Homology Modeling (HM) targets. RAPTOR was implemented at the University of Waterloo and it can be accessed at http://www.cs.uwaterloo.ca/~j3xu/RAPTOR_form.htm.

Algorithms↗
PubMed2004

Farnesylthiosalicylic acid inhibits mammalian target of rapamycin (mTOR) activity both in cells and in vitro by promoting dissociation of the mTOR-raptor complex.

The mammalian target of rapamycin (mTOR) functions with raptor and mLST8 in a signaling complex that controls rates of cell growth and proliferation. Recent results indicate that an inhibitor of the Ras signaling pathway, farnesylthiosalicylic acid (FTS), decreased phosphorylation of the mTOR effectors, PHAS-I and S6K1, in breast cancer cells. Here we show that incubating 293T cells with FTS produced a stable change in mTOR activity that could be measured in immune complex kinase assays using purified PHAS-I as substrate. Similarly, FTS decreased the PHAS-I kinase activity of mTOR when added to cell extracts or to immune complexes containing mTOR. Incubating either cells or extracts with FTS also decreased the amount of raptor that coimmunoprecipitated with mTOR, although having relatively little effect on the amount of mLST8 that coimmunoprecipitated. The concentration effect curves of FTS for inhibition of mTOR activity and for dissociation of the raptor-mTOR complex were almost identical. Caffeine, wortmannin, LY294002, and rapamycin-FKBP12 also markedly inhibited mTOR activity in vitro, but unlike FTS, none of the other mTOR inhibitors appreciably changed the amount of raptor associated with mTOR. Thus, our findings indicate that FTS represents a new type of mTOR inhibitor, which acts by dissociating the functional mTOR-raptor signaling complex.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Prevalence of encysted Toxoplasma gondii in raptors from Alabama.

Little is known about the prevalence of encysted Toxoplasma gondii in wild birds. We examined the hearts and breast muscles from 101 raptors for encysted T. gondii. All of the raptors had been submitted for necropsy to the State Veterinary Diagnostic Laboratory, Auburn, Alabama. Tissues were digested in acid-pepsin solution and inoculated into groups of 3-5 laboratory mice. Toxoplasma gondii was isolated from 27 of 101 (26.7%) raptors: 8 of 12 (66.7%) red-shouldered hawks (Buteo lineatus), 13 of 27 (41.1%) red-tailed hawks (Buteo jamaicensis), 1 of 4 (25%) Cooper's hawks (Accipiter cooperi), 1 of 5 (20%) great horned owls (Bubo virginianus), 4 of 15 (26.7%) barred owls (Strix varia), and 1 of 3 (33.3%) kestrels (Falco sparverius). Toxoplasma gondii was not isolated from 3 broad-winged hawks (Buteo platypterus), 3 sharp-shinned hawks (Accipiter striatus), 6 barn owls (Tyto alba), 9 screech owls (Asio otus), a Mississippi kite (Ictinia misisippiensis), 2 golden eagles (Aquila chrysaetos), a bald eagle (Haliaeetus leucocephalus), 4 ospreys (Pandion haliaetus), 4 turkey vultures (Cathartes aura), or 2 black vultures (Coragyps atratus). No significant difference (P > 0.05) in prevalence was detected based on sex using chi-square analysis. Chi-square analysis of the data demonstrated that adult raptors had encysted stages of T. gondii significantly (P < 0.05) more often than did immature raptors.

Age Factors↗
PubMed1998

A retrospective study of morbidity and mortality of raptors in Florida: 1988-1994.

A retrospective study was conducted on 390 raptors admitted to the University of Florida Veterinary Medical Teaching Hospital (VMTH) during 1988-1994. Representatives of 20 species were admitted; the five most common species were the barred owl (Strix varia, 72), eastern sreech owl (Otus asio, 63), red-shouldered hawk (Buteo lineatus, 49), bald eagle (Haleaeetus leucocephalus, 43), and red-tailed hawk (Buteo jamaicensis, 38). A primary clinical diagnosis was determined in 340 (87%) of the 390 raptors admitted to the VMTH; a diagnosis was not made for the remaining 50 birds. Eighty-two percent (279) had traumatic injuries, and 87% (243) of those were directly related to human activity. The primary clinical diagnoses in the remaining 61 raptors included toxicosis (21), poor nutrition (15), infectious disease (11), orphaned young (11), and electrocution (3). The disposition of the 390 raptors was as follows: 61% (237) died or euthanized, 21% (80) released to the wild, 15% (57) outcome unknown, and 4% (16) permanent captives. Necropsies were performed on 32 of the 237 raptors that died.

Animals↗
PubMed2000

Raptor therapeutics.

Developing a therapeutic plan for raptors can be challenging because the veterinarian must take numerous and sometimes conflicting factors into consideration. Successful therapy depends on proper management of the raptor patient, beginning with its initial presentation and continuing throughout its time in captivity. Important considerations concerning medicine and natural history peculiar to raptors are addressed. Guidelines for constructing an effective therapeutic plan for the treatment of common diseases and conditions seen in wild raptors are presented.

Animals↗
PubMed1998

Emergency care of raptors.

Emergency care of raptors often requires extensive diagnostics and therapeutic regimens to stabilize and support the ill or injured raptor. Whether falconry birds, educational birds, or raptors from the wild are presented, various medical conditions must be addressed to help guide the practitioner toward a complete recovery for the raptor.

Animal Husbandry↗
PubMed2002

Trypanosoma avium of raptors (Falconiformes): phylogeny and identification of vectors.

Avian trypanosomes are widespread parasites of birds, the transmission of which remains mostly unclear, with various blood-sucking insects mentioned as possible vectors. A search for vectors of trypanosomes of sparrowhawk (Accipiter nisus), buzzard (Buteo buteo), lesser-spotted eagle (Aquila pomarina) and kestrel (Falco tinnunculus) was performed in Czech and Slovak Republics. Black flies (Eusimulium spp.), hippoboscid flies (Ornithomyia avicularia), mosquitoes (Culex pipiens pipiens) and biting midges (Culicoides spp.), trapped while attempting to feed on raptor nestlings, were found to contain trypanosomatids in their intestine. Trypanosomes from the raptors and blood-sucking insects were isolated, and their 18S rRNA sequences were used for species identification and for the inference of intra- and interspecific relationships. Together with the trypanosome isolated from a black fly, the bird trypanosomes formed a well-supported Trypanosoma avium clade. The isolates derived from hippoboscid flies and mosquitoes are most likely also avian trypanosomes infecting birds other than the studied raptors. Analysis of the kinetoplast, that has features characteristic for the avian trypanosomes (minicircle size; dimensions of the kinetoplast disc), provided further evidence for the identification of vectors. It is suggested that all trypanosomes isolated from raptors included in this study belong to the T. avium complex and are transmitted by the ornithophilic simuliids such as Eusimulium securiforme.

Animals↗
PubMed2000

Habitat loss and raptor predation: disentangling long- and short-term causes of red grouse declines.

The number of red grouse (Lagopus lagopus scoticus) shot in the UK has declined by 50% during the 20th century This decline has coincided with reductions in the area of suitable habitat and recoveries in the populations of some avian predators. Here we use long-term records of shooting bags and a large-scale manipulation of raptor density to disentangle the effects of habitat loss and raptor predation on grouse populations. The numbers of grouse harvested on the Eskdale half of Langholm Moor in southern Scotland declined significantly during 1913-1990 and grouse bags from the whole moor from 1950 to 1990 exhibited an almost identical but non-significant trend. Hen harriers (Circus cyaneus) and peregrine falcons (Falco peregrinus) were absent or bred at low densities on this moor throughout this period but heather-dominant vegetation declined by 48% between 1948 and 1988. Harrier and peregrine breeding numbers on Langholm Moor increased to high levels following protection in 1990 whilst grouse density and grouse bags declined year after year until shooting was abandoned in 1998. The prediction of a peak in grouse bags on Langholm Moor in 1996 based on the patterns of bags during 1950-1990 was supported by the observed peaks in 1997 on two nearby moors with few raptors which formerly cycled in synchrony with Langholm Moor. This study demonstrates that, whilst long-term declines in grouse bags were most probably due to habitat loss, high levels of raptor predation subsequently limited the grouse population and suppressed a cycle. This study thus offers support to theoretical models which predict that generalist predators may suppress cycles in prey populations.

Animals↗
PubMed2001

A retrospective study of the success of medical and surgical treatment of wild Australian raptors.

OBJECTIVE: To evaluate the results of medical and surgical regimens utilised to treat injured and diseased wild Australian raptors presented at our practice, and to determine if the time, effort and cost of treating the birds was justified in terms of the outcomes achieved. PROCEDURE: All the practice's clinical records relating to the examination and treatment of wild raptors were reviewed for the period April 1994 to December 1998. The species of birds, the aetiology of their injuries or diseases, the treatment protocols and the outcomes of those treatments were correlated and tabulated for evaluation. RESULTS: Fifteen Australian species of raptor were examined and treated. Complete records were available for 104 birds of prey, 73 being Accipitriformes and 31 Strigiformes. The poorest prognosis was for birds involved in motor vehicle impacts, while birds suffering malnutrition or starvation had higher survival rates. The overall rate of survival was 50%. CONCLUSION: Based on the severity of diseases and injuries at the time of presentation, the survival rate was considered acceptable. Veterinary involvement in the treatment of the wild raptors was necessary for the maintenance of the birds' welfare, and to determine appropriate treatments. Intangible benefits included increased practice staff satisfaction, and improving the veterinary professions' public image by providing pro bono treatment for Australian wildlife.

Animals↗
PubMed2004

Raptor and mTOR: subunits of a nutrient-sensitive complex.

mTOR/RAFT1/FRAP is the target of the FKBP12-rapamycin complex as well as a central component of a nutrient- and hormone-sensitive pathway that controls cellular growth. Recent work reveals that mTOR interacts with a novel evolutionarily conserved protein that we named raptor, for "regulatory associated protein of mTOR." Raptor has several roles in the mTOR pathway. It is necessary for nutrient-mediated activation of the downstream effector S6K1 and increases in cell size. In addition, under conditions that repress the mTOR pathway, the association of raptor with mTOR is strengthened, leading to a decrease in mTOR kinase activity. Raptor is a critical component of the mTOR pathway that regulates cell growth in response to nutrient levels by associating with mTOR.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Environmental exposure and distribution of lead in four species of raptors in Southeastern Spain.

The purpose of this study was to monitor exposure to lead in four species of raptors in Southeastern Spain (Murcia Region). Samples of liver, kidney, brain, blood, and bone from two species of diurnal raptors (European kestrel (Falco tinnunculus) and European buzzard (Buteo buteo)) and two species of nocturnal raptors (Eagle owl (Bubo bubo) and Little owl (Athene noctua)) were obtained during 1994. Relationships were found between size and age of the birds, the nearness to areas of human activity and lead concentrations in tissues. The lead distribution pattern reveals that the bone is the principle organ for accumulation (0.62-43 mg/Kg, dry weight), followed by the kidney (0.03-0.66 mg/Kg, wet weight), and liver (0. 017-0.05 mg/Kg, w.w.), and to lesser extent, the brain (0.013-0.223 mg/Kg, w.w.). This distribution pattern indicates that raptors in Southeastern Spain were exposed to environmental low lead levels continuously over an extended period of time. Correlations between lead in bone and lead in soft tissues were higher in European buzzards (r = 0.87-0.95) and Eagle owl (r = 0.71-0.86) than those found in European kestrels (r = 0.53-0.58) and Little owls (r << 0). However, correlations between lead concentrations in soft tissues and in blood were high (r = 0.85-0.99).

Animals↗
PubMed2004

Raptor, a binding partner of target of rapamycin.

The mammalian target of rapamycin (mTOR) controls cell growth in response to amino acids and growth factors, in part by regulating p70 S6 kinase alpha (p70 alpha) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). Raptor (regulatory associated protein of mTOR) is a 150 kDa mTOR binding protein that is essential for TOR signaling in vivo and also binds 4EBP1 and p70alpha through their respective TOS (TOR signaling) motifs, a short conserved segment previously shown to be required for amino acid- and mTOR-dependent regulation of these substrates in vivo. Raptor appears to serve as an mTOR scaffold protein, the binding of which to the TOS motif of mTOR substrates is necessary for effective mTOR-catalyzed phosphorylation. Further understanding of regulation of the mTOR-raptor complex in response to the nutritional environment would require identification of the interplay between the mTOR-raptor complex and its upstream effectors such as the protein products of tumor suppressor gene tuberous sclerosis complexes 1 and 2, and the Ras-related small G protein Rheb.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1.

The mTOR kinase controls cell growth, proliferation, and survival through two distinct multiprotein complexes, mTORC1 and mTORC2. mTOR and mLST8 are in both complexes, while raptor and rictor are part of only mTORC1 and mTORC2, respectively. To investigate mTORC1 and mTORC2 function in vivo, we generated mice deficient for raptor, rictor, or mLST8. Like mice null for mTOR, those lacking raptor die early in development. However, mLST8 null embryos survive until e10.5 and resemble embryos missing rictor. mLST8 is necessary to maintain the rictor-mTOR, but not the raptor-mTOR, interaction, and both mLST8 and rictor are required for the hydrophobic motif phosphorylation of Akt/PKB and PKCalpha, but not S6K1. Furthermore, insulin signaling to FOXO3, but not to TSC2 or GSK3beta, requires mLST8 and rictor. Thus, mTORC1 function is essential in early development, mLST8 is required only for mTORC2 signaling, and mTORC2 is a necessary component of the Akt-FOXO and PKCalpha pathways.

Animals↗
PubMed2003

The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif.

The mammalian target of rapamycin (mTOR) controls multiple cellular functions in response to amino acids and growth factors, in part by regulating the phosphorylation of p70 S6 kinase (p70S6k) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Raptor (regulatory associated protein of mTOR) is a recently identified mTOR binding partner that also binds p70S6k and 4E-BP1 and is essential for TOR signaling in vivo. Herein we demonstrate that raptor binds to p70S6k and 4E-BP1 through their respective TOS (conserved TOR signaling) motifs to be required for amino acid- and mTOR-dependent regulation of these mTOR substrates in vivo. A point mutation of the TOS motif also eliminates all in vitro mTOR-catalyzed 4E-BP1 phosphorylation and abolishes the raptor-dependent component of mTOR-catalyzed p70S6k phosphorylation in vitro. Raptor appears to serve as an mTOR scaffold protein, the binding of which to the TOS motif of mTOR substrates is necessary for effective mTOR-catalyzed phosphorylation in vivo and perhaps for conferring their sensitivity to rapamycin and amino acid sufficiency.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Two motifs in the translational repressor PHAS-I required for efficient phosphorylation by mammalian target of rapamycin and for recognition by raptor.

Mammalian target of rapamycin (mTOR) is the central element of a signaling pathway involved in the control of mRNA translation and cell growth. The actions of mTOR are mediated in part through the phosphorylation of the eukaryotic initiation factor 4E-binding protein, PHAS-I. In vitro mTOR phosphorylates PHAS-I in sites that control PHAS-I binding to eukaryotic initiation factor 4E; however, whether mTOR directly phosphorylates PHAS-I in cells has been a point of debate. The Arg-Ala-Ile-Pro (RAIP motif) and Phe-Glu-Met-Asp-Ile (tor signaling motif) sequences found in the NH2- and COOH-terminal regions of PHAS-I, respectively, are required for the efficient phosphorylation of PHAS-I in cells. Here we show that mutations in either motif markedly decreased the phosphorylation of recombinant PHAS-I by mTOR in vitro. Wild-type PHAS-I, but none of the mutant proteins, was coimmunoprecipitated with hemagglutinin-tagged raptor, an mTOR-associated protein, after extracts of cells overexpressing raptor had been supplemented with recombinant PHAS-I proteins. Moreover, raptor overexpression enhanced the phosphorylation of wild-type PHAS-I by mTOR but not the phosphorylation of the mutant proteins. The results not only provide direct evidence that both the RAIP and tor signaling motifs are important for the phosphorylation by mTOR, possibly by allowing PHAS-I binding to raptor, but also support the view that mTOR phosphorylates PHAS-I in cells.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Chlamydiosis in captive raptors.

Chlamydia psittaci was isolated from four red-tailed hawks (Buteo jamaicensis) that died suddenly and from seven birds that survived at a raptor rehabilitation center in California in 1983. One hundred captive raptors representing 14 species in five families were subsequently tested serologically and by direct cloacal culture. C. psittaci was isolated from seven clinically normal birds. Forty-four percent of the raptors were considered positive using an enzyme-linked immunosorbent assay (ELISA), and 19% were suspects. The ELISA was repeated on 54 raptors in 1986. Forty-one percent of the birds were considered positive, and 35% were suspect, indicating that C. psittaci is endemic in the population.

Animals↗
PubMed2004

Competitive interactions among raptors in boreal forests.

We examined inter-specific interactions among goshawks ( Accipiter gentilis), common buzzards (Buteo buteo) and honey buzzards (Pernis apivorus) in western Finland in 1983-1996. Because goshawks are among the largest birds of prey species in boreal forests they may take over the nest of smaller and less-competitive forest-dwelling raptors when searching for suitable places for breeding. Accordingly, more than half of newly established goshawk territories were found on the territories previously occupied by the common buzzard and the honey buzzard. Otherwise, territory sharing between these species was rare. Fledgling production of honey buzzards was not associated with the presence of goshawks, probably owing to the almost 2 months later onset of breeding. This probably decreases competitive interactions between these two species. An intensive interference competition, instead, seemed to be evident between common buzzards and goshawks, because the fledgling production of common buzzards was decreased by 20% as a result of failures during incubation and nestling period in the vicinity (<1 km) of occupied goshawk nests. Similarly, territory occupancy of common buzzards till the next breeding season was significantly reduced in the presence of goshawks. Relatively high proportions of occupied buzzard territories (17%) in the study area were shared by breeding goshawks on the same territory. This suggests that although their diets are dissimilar they inhabit similar habitats and might compete for the available prime nesting habitats within forest landscapes. In addition, goshawks benefit from taking over the complete nests of other raptors, imposing upon the original owners of the nest, because building a large stick nest is probably energetically costly. As a large raptor, the goshawk apparently has a competitive advantage over smaller ones, and may have an ever-increasing impact on smaller birds of prey, if there is a lack of sheltered forests inducing competition for the available nest sites.

Animals↗