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PubMed2000

Mutations modulating the Argos-regulated signaling pathway in Drosophila eye development.

Argos is a secreted protein that contains an EGF-like domain and acts as an inhibitor of Drosophila EGF receptor activation. To identify genes that function in the Argos-regulated signaling pathway, we performed a genetic screen for enhancers and suppressors of the eye phenotype caused by the overexpression of argos. As a result, new alleles of known genes encoding components of the EGF receptor pathway, such as Star, sprouty, bulge, and clown, were isolated. To study the role of clown in development, we examined the eye and wing phenotypes of the clown mutants in detail. In the eye discs of clown mutants, the pattern of neuronal differentiation was impaired, showing a phenotype similar to those caused by a gain-of-function EGF receptor mutation and overexpression of secreted Spitz, an activating ligand for the EGF receptor. There was also an increased number of pigment cells in the clown eyes. Epistatic analysis placed clown between argos and Ras1. In addition, we found that clown negatively regulated the development of wing veins. These results suggest that the clown gene product is important for the Argos-mediated inhibition of EGF receptor activation during the development of various tissues. In addition to the known genes, we identified six mutations of novel genes. Genetic characterization of these mutants suggested that they have distinct roles in cell differentiation and/or survival regulated by the EGF receptor pathway.

Animals↗
PubMed1994

Evaluation of the Roche Cobas Argos 5Diff automated haematology analyser with comparison to a Coulter STKS.

The performance of the Roche Cobas Argos 5Diff (Argos) automated haematology analyser was evaluated by comparison to manual blood film examination and a Coulter STKS (STKS) analyser. The Argos demonstrated excellent between and inter-batch imprecision for all parameters, except the MCHC, and good linearity for Hb, WBC and platelet count (PLT). After an initial fall the PLT, results were stable for up to six h at 18 degrees C in EDTA(K3) after which an increasing proportion of cells were classified as lymphocytes. Results of 239 patient samples analysed on both instruments, compared by linear regression, gave excellent correlation (r2 > 0.90) for most parameters with the exceptions of the MCHC (0.317), eosinophils% (0.756), monocytes% (0.48) and basophils% (0.002). 'Flagging' of cellular abnormalities by the Argos resulted in excellent sensitivity (97.5%), specificity (93.2%) and efficiency/agreement (93.2%), with fewer false positive and negative results than the STKS, although these differences were not statistically significant. The performance characteristics of the Argos were comparable to those of the STKS with a possible improvement in its flagging abilities.

Autoanalysis↗
PubMed1992

The argos gene encodes a diffusible factor that regulates cell fate decisions in the Drosophila eye.

The argos gene encodes a protein that is required for viability and that regulates the determination of cells in the Drosophila eye. A developmental analysis of argos mutant eyes indicates that the mystery cells, which are usually nonneuronal, are transformed into extra photoreceptors, and that supernumerary cone cells and pigment cells are also recruited. Clonal analysis indicates that argos acts nonautonomously and can diffuse over the range of several cell diameters. Conceptual translation of the argos gene suggests that it encodes a secreted protein.

Amino Acid Sequence↗
PubMed1995

Inhibition of Drosophila EGF receptor activation by the secreted protein Argos.

The Drosophila homologue of the mammalian epidermal growth factor (EGF) receptor (DER) is a receptor tyrosine kinase involved in many stages of fly development, including photoreceptor determination, and wing-vein formation. Its primary activating ligand is the Spitz protein, which is similar to mammalian TGF-alpha. Argos is a secreted protein that, like Spitz, contains a single EGF motif. It is a repressor of cell determination in the eye, and acts in other tissues, including the wing. Because Argos has the opposite effects to DER in the eye (the former blocks photoreceptor determination, the latter promotes it) we have tested whether it acts by blocking the DER pathway. We show that Argos does indeed repress this pathway in vivo and find that, in vitro, Argos protein can inhibit the activation of DER by Spitz. Thus the determination of cells by the DER pathway is regulated by a balance between extracellular activating and inhibiting signals. This is the first in vivo example of an extracellular inhibitor of a receptor tyrosine kinase.

Animals↗
PubMed1998

Argos induces programmed cell death in the developing Drosophila eye by inhibition of the Ras pathway.

We studied the role of Ras signaling in the regulation of cell death during Drosophila eye development. Overexpression of Argos, a diffusible inhibitor of the EGF receptor and Ras signaling, caused excessive cell death in developing eyes at pupal stages. The Argos-induced cell death was suppressed by coexpression of the anti-apoptotic genes p35, diap1, or diap2 in the eye as well as by the Df(3L)H99 chromosomal deletion that lacks three apoptosis-inducing genes, reaper, head involution defective (hid) and grim. Transient misexpression of the activated Ras1 protein (Ras1V12) later in pupal development suppressed the Argos-induced cell death. Thus, Argos-induced cell death seemed to have resulted from the suppression of the anti-apoptotic function of Ras. Conversely, cell death induced by overexpression of Hid was suppressed by gain-of-function mutations of the genes coding for MEK and ERK. These results support the idea that Ras signaling functions in two distinct processes during eye development, first triggering the recruitment of cells and later negatively regulating cell death.

Animals↗
PubMed1995

Evaluation of the leukocyte differential flags on an hematologic analyzer. The Cobas Argos 5 Diff.

To evaluate the leukocyte differential flags of the Cobas Argos 5 Diff., the authors performed a comparative study between their current analyzer, the Technicon H2, and the manual leukocyte differential. Samples (n = 1,600) were collected from the Blood Disease Department of their hospital and were tested on both Cobas Argos 5 Diff. (ABX/Roche Hematology Division, Montpellier, France) and Technicon H2. Abnormalities of the manual leukocyte differential (immature granulocytes, blast cells, atypical lymphocytes, hyperbasophil cells, erythroblasts, and hairy cells) were found in 597 samples. The authors determined the best cut-off of the quantitative flags--atypical lymphocytes (ALYs) and large immature cells (LICs)--using the likelihood ratio method, and the capability of the 5 Diff. qualitative flags to determine abnormal subpopulations by the predictive value of a positive result. The presence of particular combinations of flags was associated with band cells and blast cells of acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML). The sensitivity, specificity, and efficiency of the two analyzers were 92.1, 53.9, and 68.2, respectively, for the Argos 5 Diff., and 93.5, 36.7 and 57.9, respectively, for Technicon H2. In conclusion, the Cobas Argos 5 Diff. is well adapted for detecting leukocyte abnormalities.

Data Interpretation, Statistical↗
PubMed2002

THE DIET OF PLATYDORIS ARGO (GASTROPODA: NUDIBRANCHIA) AND THE DIETARY SPECIALIZATION OF SPONGE EATING DORIDS.

The diet of the dorid nudibranch Platydoris argo was studied in relation to prey availability, and under different environmental conditions to evaluate richness, evenness, and plasticity of its diet. In order to assess the availability of possible prey, the sponge assemblage at two different habitats was characterized. The results showed that P. argo is a relatively specialized benthic carnivore, feeding exclusively on spiculated demosponges. However, it has a relatively polyphagous diet (16 prey-species) and adapts well to contrasting patterns of prey availability at different sites. At the location with lower sponge diversity, the diet of P. argo included more prey categories, was more diverse, and less selective (lower dietary evenness), foraging preferentially on the most frequent resource, Stylopus dujardini. In contrast, at a station with a clearly more diverse and abundant sponge assemblage, the diet was more selective, and Phorbas tenacior was its principal component. Despite its trophic plasticity, P. argo displayed a specialized pattern of resource exploitation in terms of niche breadth within a given habitat. Foraging was focussed on one preferred prey (which changed from one habitat to another) as indicated by the significant positive selection indexes (S. dujardini = +0.29, P. tenacior = +0.74). The revision of quantitative data on the diet of so-called 'sponge eating dorids' indicates the existence of a more specialized guild of 'spiculated demosponge eating dorids'. Most species revised are 'non-stereotyped specialist', which indicates that they have a polyphagous and plastic diet but only exploit one or few main prey species in each habitat. However, obligate specialists, with a monophagous (or rather oligophagous) diet also seem to be present.

Journal Article↗
PubMed2005

ARGO: a web system for the detection of degenerate motifs and large-scale recognition of eukaryotic promoters.

Reliable recognition of the promoters in eukaryotic genomes remains an open issue. This is largely owing to the poor understanding of the features of the structural-functional organization of the eukaryotic promoters essential for their function and recognition. However, it was demonstrated that detection of ensembles of regulatory signals characteristic of specific promoter groups increases the accuracy of promoter recognition and prediction of specific expression features of the queried genes. The ARGO_Motifs package was developed for the detection of sets of region-specific degenerate oligonucleotide motifs in the regulatory regions of the eukaryotic genes. The ARGO_Viewer package was developed for the recognition of tissue-specific gene promoters based on the presence and distribution of oligonucleotide motifs obtained by the ARGO_Motifs program. Analysis and recognition of tissue-specific promoters in five gene samples demonstrated high quality of promoter recognition. The public version of the ARGO system is available at http://wwwmgs2.bionet.nsc.ru/argo/ and http://emj-pc.ics.uci.edu/argo/.

Algorithms↗
PubMedDate not supplied

Assessment of functional capacity during gait using a reciprocal propulsion orthosis (ARGO)--a comparative study with a conventional mechanical orthosis.

One subject (male, 24 years) with an incomplete motor and sensitive SCI, neurological level C6-C7 was submitted to a comparative study during gait using an advanced reciprocating gait othosis (ARGO) and a conventional mechanical orthosis (CMO) and respiratory and metabolic variables were compared at peak effort and in the second minute of recovery. We found that the ARGO, as with the CMO, not guarantee gait independence but the ARGO does enable a more functional gait pattern with a more efficient ventilation. The ratio of CO2/O2 showed that ARGO enable aerobic conditions of work and the energy expenditure using is significantly lower than CMO.

Adult↗
PubMed2003

A prototype of an adjustable advanced reciprocating gait orthosis (ARGO) for spinal cord injury (SCI).

OBJECTIVE: To develop a reciprocating gait orthosis which could be used in different sized patients. DESIGN: Clinical trial and orthotic development. SETTING: A large rehabilitation hospital in Rome, Italy PATIENTS AND METHODS: To carry out this project normal reciprocating gait orthosis parts were used. The device was modified to adjust the hip-ankle height, and the hip-hip distance. It was tested, by five patients already walking with standard ARGO, to evaluate the performances of the orthosis. The device has been tested on seven newly injured patients fulfilling specific criteria of different height and weight. MAIN OUTCOME MEASURES: Prototype suitability; patients appreciation. RESULTS: The device can be used for persons between 1.60 m and 1.85 m tall, weighing up to 100 kg. The orthosis allows an upright position without the use of the hands, and walking with a walker or with two canes. The foot orthosis cover sizes 36-40 (British 3-7) and 41-45 (British 7-11). With the exception of donning, doffing and lifting, the walking performances of the prototype and the general appreciation is comparable with those of a standard device. After a short period of training all seven patients were able to walk in the parallel bars. All of them expressed general appreciation for the device; despite this only four patients wanted the orthosis, two refused it and one has not decided yet. CONCLUSIONS: The prototype allows the same standing and walking performances of normal ARGO. It could be used in spinal cord injury patients to let them test the potential of the device and thus be useful in the effort to reduce the percentage of ARGO rejection.

Adolescent↗
PubMed1998

Walking with the advanced reciprocating gait orthosis (ARGO) in thoracic paraplegic patients: energy expenditure and cardiorespiratory performance.

The aim of this study was to quantify the energy cost and the cardiorespiratory response while walking at free speed with an Advanced Reciprocating Gait Orthosis (ARGO). The study was conducted on a group of six male paraplegic patients, age range 16-31 years (median = 22.50), with complete traumatic injuries ranging from T3 to T12 and a median time lapse from the trauma of 21 months. The data was recorded 6-8 weeks after the patients were fitted and trained to use the orthosis. Maintaining a standing position produced a significant increase of both the heart rate (HR) and the respiratory rate (RR), whilst the increase of energy consumption was not significant. The data for median speed, energy consumption and energy cost observed during free walking was similar to that of the Reciprocating Gait Orthosis (RGO) in thoracic level paraplegic individuals. This study indicates that in the utilisation of the ARGO the workload is not excessive when it is limited to maintaining a standing position. In contrast, walking results in early anaerobic conditions and unsustainable fatigue after short distances. The great energy cost recorded is considered to be a main reason for the frequent abandonment or the low utilisation of the orthosis at follow-up.

Adolescent↗
PubMed2006

The Arabidopsis ARGOS-LIKE gene regulates cell expansion during organ growth.

Cell expansion, and its coordination with cell division, plays a critical role in the growth and development of plant organs. However, the genes controlling cell expansion during organogenesis are largely unknown. Here, we demonstrate that a novel Arabidopsis gene, ARGOS-LIKE (ARL), which has some sequence homology to the ARGOS gene, is involved in this process. Reduced expression or overexpression of ARL in Arabidopsis results in smaller or larger cotyledons and leaves as well as other lateral organs, respectively. Anatomical examination of cotyledons and leaves in ARL transgenic plants demonstrates that the alteration in size can be attributed to changes in cell size rather than cell number, indicating that ARL plays a role in cell expansion-dependent organ growth. ARL is upregulated by brassinosteroid (BR) and this induction is impaired in the BR-insensitive mutant bri1, but not in the BR-deficient mutant det2. Ectopic expression of ARL in bri1-119 partially restores cell growth in cotyledons and leaves. Our results suggest that ARL acts downstream of BRI1 and partially mediates BR-related cell expansion signals during organ growth.

Amino Acid Sequence↗
PubMed2004

Evidence for an arginine exporter encoded by yggA (argO) that is regulated by the LysR-type transcriptional regulator ArgP in Escherichia coli.

The anonymous open reading frame yggA of Escherichia coli was identified in this study as a gene that is under the transcriptional control of argP (previously called iciA), which encodes a LysR-type transcriptional regulator protein. Strains with null mutations in either yggA or argP were supersensitive to the arginine analog canavanine, and yggA-lac expression in vivo exhibited argP(+)-dependent induction by arginine. Lysine supplementation phenocopied the argP null mutation in that it virtually abolished yggA expression, even in the argP+ strain. The dipeptides arginylalanine and lysylalanine behaved much like arginine and lysine, respectively, to induce and to turn off yggA transcription. Dominant missense mutations in argP (argPd) that conferred canavanine resistance and rendered yggA-lac expression constitutive were obtained. The protein deduced to be encoded by yggA shares similarity with a basic amino acid exporter (LysE) of Corynebacterium glutamicum, and we obtained evidence for increased arginine efflux from E. coli strains with either the argPd mutation or multicopy yggA+. The null yggA mutation abolished the increased arginine efflux from the argPd strain. Our results suggest that yggA encodes an ArgP-regulated arginine exporter, and we have accordingly renamed it argO (for "arginine outward transport"). We propose that the physiological function of argO may be either to prevent the accumulation to toxic levels of canavanine (which is a plant-derived antimetabolite) or arginine or to maintain an appropriate balance between the intracellular lysine and arginine concentrations.

Arginine↗
PubMed2005

Fine-scale tracking of marine turtles using GPS-Argos PTTs.

High-accuracy location data of wildlife telemetry using conventional satellite location systems are difficult to obtain. However, such data are necessary to clarify the nature of movements and home range sizes of animals. In order to measure the high-accuracy location data, we developed new GPS-Argos Platform Terminal Transmitters (PTTs) which transmit both the conventional location and GPS location simultaneously. Two experiments, one in an artificial rearing pond and the other in the open sea, were performed. First, two hawksbill turtles were tracked with the PTTs in a 5 ha breeding pond in Thailand. Their home ranges using both data were calculated and found to be 2.96 ha and 0.93 ha by the GPS data, and 156,740 ha and 184,478 ha by a conventional data. Secondly, a female green turtle attached with the GPS-Argos was released from the coast of Pangnga Province, Thailand. There was a relationship between depth and speed of travel based on the GPS data. The data from the PTT showed that the turtle moved south along the coastline at the depth of less than 20 m for 5 days, and then stayed at a depth of less than 10 m for 4 days. However, we could not find any clear relationship using conventional data. Only a meandering movement at a variety of depths was observed. The results of the two experiments indicated the PTTs have an enormous potential for enhancing our understanding of fine-scale movement patterns and home ranges of marine turtles.

Animals↗
PubMed2005

Lozenge directly activates argos and klumpfuss to regulate programmed cell death.

We show that reducing the activity of the Drosophila Runx protein Lozenge (Lz) during pupal development causes a decrease in cell death in the eye. We identified Lz-binding sites in introns of argos (aos) and klumpfuss (klu) and demonstrate that these genes are directly activated targets of Lz. Loss of either aos or klu reduces cell death, suggesting that Lz promotes apoptosis at least in part by regulating aos and klu. These results provide novel insights into the control of programmed cell death (PCD) by Lz during Drosophila eye development.

Animals↗
PubMed2000

The interaction between the Drosophila secreted protein argos and the epidermal growth factor receptor inhibits dimerization of the receptor and binding of secreted spitz to the receptor.

Drosophila Argos (Aos), a secreted protein with an epidermal growth factor (EGF)-like domain, has been shown to inhibit the activation of the Drosophila EGF receptor (DER). However, it has not been determined whether Aos binds directly to DER or whether regulation of the DER activation occurs through some other mechanism. Using DER-expressing cells (DER/S2) and a recombinant DER extracellular domain-Fc fusion protein (DER-Fc), we have shown that Aos binds directly to the extracellular domain of DER with its carboxyl-terminal region, including the EGF-like domain. Furthermore, Aos can block the binding of secreted Spitz (sSpi), a transforming growth factor alpha-like ligand of DER, to the extracellular domain of DER. We observed that sSpi stimulates the dimerization of both the soluble DER extracellular domain (sDER) and the intact DER in the DER/S2 cells and that Aos can block the sSpi-induced dimerization of both sDER and intact DER. Moreover, we have shown that, by directly interacting with DER, Aos and SpiAos (a chimeric protein that is composed of the N-terminal region of Spi and the C-terminal region of Aos) inhibit the dimerization and phosphorylation of DER that are induced by DER's overexpression in the absence of sSpi. These results indicate that Aos exerts its inhibitory function through dual molecular mechanisms: by blocking both the receptor dimerization and the binding of activating ligand to the receptor. This is the first description of this novel inhibitory mechanism for receptor tyrosine kinases.

Animals↗
PubMed1999

The Drosophila dead ringer gene is required for early embryonic patterning through regulation of argos and buttonhead expression.

The dead ringer (dri) gene of Drosophila melanogaster is a member of the recently discovered ARID-box family of eukaryotic genes that encode proteins with a conserved DNA binding domain. dri itself is highly conserved, with specific orthologs in the human, mouse, zebrafish and C. elegans genomes. We have generated dri mutant alleles to show that dri is essential for anterior-posterior patterning and for muscle development in the embryo. Consistent with the mutant phenotype and the sequence-specific DNA-binding properties of its product, dri was found to be essential for the normal early embryonic expression pattern of several key regulatory genes. In dri mutant embryos, expression of argos in the terminal domains was severely reduced, accounting for the dri mutant head phenotype. Conversely, buttonhead expression was found to be deregulated in the trunk region, accounting for the appearance of ectopic cephalic furrows. Curiously, dri was found also to be required for maintenance of expression of the ventrolateral region of even-skipped stripe four. This study establishes dri as an essential co-factor in the regulated expression of specific patterning genes during early embryogenesis.

Animals↗
PubMed2005

Venlafaxine extended release versus conventional antidepressants in the remission of depressive disorders after previous antidepressant failure: ARGOS study.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) may be used as an alternative treatment for depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant. This randomized, open-label, multicenter study compared the effectiveness of the SNRI venlafaxine extended release (VXR) with that of conventional antidepressants (CA) in patients who were referred to an outpatient psychiatric specialty care setting for treatment after failure to tolerate or respond to at least 4 weeks of treatment with a CA in a primary care setting. Patients with a Hamilton Depression Rating Scale (HAM-D17) score > or =17 were randomly assigned to treatment with an alternative CA or VXR. Remission was defined as a score < or =7 on the HAM-D17. Efficacy analyses were carried out on 3,097 patients from the intent-to-treat (ITT) population (1,632 VXR; 1,465 CA). The antidepressants prescribed most frequently in the CA group were paroxetine (21.3%), citalopram (20.1%), sertraline (19.1%), fluoxetine (17.0%), and mirtazapine (7.9%). After 24 weeks of treatment, the VXR group demonstrated a significantly higher remission rate than did the CA group (59.3% VXR; 51.5% CA; P<.0001; odds ratio: 1.37; 95% CI: 1.19-1.58; P<.01). Despite the limitations of the open design, the results of this study suggest that venlafaxine extended release may be more effective than the conventional antidepressants used in this study when treating depressed patients who do not tolerate or respond adequately to treatment with a conventional antidepressant.

Adolescent↗