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At least 433 records · Page 24Linked to original sources
PubMed1992

A Drosophila rotund transcript expressed during spermatogenesis and imaginal disc morphogenesis encodes a protein which is similar to human Rac GTPase-activating (racGAP) proteins.

The rotund (rn) locus of Drosophila melanogaster at cytogenetic position 84D3,4 has been isolated and cloned on the basis of the mutant phenotype: an absence of structures in the subdistal regions of the appendages. The shortened appendages are the consequence of a localized cell death in the imaginal discs, precursors of the adult appendages. Physical characterization of the rn locus has demonstrated that it is relatively large, occupying a minimum of 50 kb. There are two major transcripts of 1.7 kb (m1.7) and 5.3 kb (m5.3). We present here the sequence analysis of m1.7 and its putative product, rnprot1.7, and show that rnprot1.7 is similar to the product of the human n-chimaerin gene, which is expressed in brain and testes. Recently, the GAP activity of n-chimaerin was demonstrated and shown to be specific for the Rac subfamily of the Ras oncoproteins. The Rac proteins have been implicated in the regulation of secretory processes. In addition to being expressed in the imaginal discs, the m1.7 racGAP transcript was detected in developmentally specific germ line cells of the testes, the primary spermatocytes.

Amino Acid Sequence↗
PubMed1999

The levels of the bancal product, a Drosophila homologue of vertebrate hnRNP K protein, affect cell proliferation and apoptosis in imaginal disc cells.

We have characterized the Drosophila bancal gene, which encodes a Drosophila homologue of the vertebrate hnRNP K protein. The bancal gene is essential for the correct size of adult appendages. Reduction of appendage size in bancal mutant flies appears to be due mainly to a reduction in the number of cell divisions in the imaginal discs. Transgenes expressing Drosophila or human hnRNP K are able to rescue weak bancal phenotype, showing the functional similarity of these proteins in vivo. High levels of either human or Drosophila hnRNP K protein in imaginal discs induces programmed cell death. Expression of the antiapoptotic P35 protein suppresses this phenotype in the eye, suggesting that apoptosis is the major cellular defect caused by overexpression of K protein. Finally, the human K protein acts as a negative regulator of bancal gene expression. We propose that negative autoregulation limits the level of Bancal protein produced in vivo.

Amino Acid Sequence↗
PubMed1999

Targeted expression of the DNA binding domain of DRE-binding factor, a Drosophila transcription factor, attenuates DNA replication of the salivary gland and eye imaginal disc.

The promoters of Drosophila genes encoding DNA replication-related proteins contain transcription regulatory elements consisting of an 8-bp palindromic DNA replication-related element (DRE) sequence (5'-TATCGATA). The specific DRE-binding factor (DREF), a homodimer of the polypeptide with 709 amino acid residues, is a positive trans-acting factor for transcription of DRE-containing genes. Both DRE binding and dimer formation are associated with residues 16 to 115 of the N-terminal region. We have established transgenic flies expressing the full-length DREF polypeptide or its N-terminal fragment (amino acid residues 1 to 125) under the control of the heat shock promoter, the salivary gland-specific promoter, or the eye imaginal disc-specific promoter. Heat shock induction of the N-terminal fragment during embryonic, larval, or pupal stages caused greater than 50% lethality. This lethality was overcome by coexpression of the full-length DREF. In salivary glands of the transgenic larvae expressing the N-terminal fragment, this fragment formed a homodimer and a heterodimer with the endogenous DREF. Ectopic expression of the N-terminal fragment in salivary gland cells reduced the contents of mRNAs for the 180-kDa subunit of DNA polymerase alpha and for dE2F and the extent of DNA endoreplication. Ectopic expression of the N-terminal fragment in the eye imaginal discs significantly reduced DNA replication in cells at the second mitotic wave. The lines of evidence suggest that the N-terminal fragment can impede the endogenous DREF function in a dominant negative manner and that DREF is required for normal DNA replication in both mitotic cell cycle and endo cycle.

Animals↗
PubMed2001

Ectopic expression of DREF induces DNA synthesis, apoptosis, and unusual morphogenesis in the Drosophila eye imaginal disc: possible interaction with Polycomb and trithorax group proteins.

The promoters of Drosophila genes encoding DNA replication-related proteins contain transcription regulatory element DRE (5'-TATCGATA) in addition to E2F recognition sites. A specific DRE-binding factor, DREF, positively regulates DRE-containing genes. In addition, it has been reported that DREF can bind to a sequence in the hsp70 scs' chromatin boundary element that is also recognized by boundary element-associated factor, and thus DREF may participate in regulating insulator activity. To examine DREF function in vivo, we established transgenic flies in which ectopic expression of DREF was targeted to the eye imaginal discs. Adult flies expressing DREF exhibited a severe rough eye phenotype. Expression of DREF induced ectopic DNA synthesis in the cells behind the morphogenetic furrow, which are normally postmitotic, and abolished photoreceptor specifications of R1, R6, and R7. Furthermore, DREF expression caused apoptosis in the imaginal disc cells in the region where commitment to R1/R6 cells takes place, suggesting that failure of differentiation of R1/R6 photoreceptor cells might cause apoptosis. The DREF-induced rough eye phenotype was suppressed by a half-dose reduction of the E2F gene, one of the genes regulated by DREF, indicating that the DREF overexpression phenotype is useful to screen for modifiers of DREF activity. Among Polycomb/trithorax group genes, we found that a half-dose reduction of some of the trithorax group genes involved in determining chromatin structure or chromatin remodeling (brahma, moira, and osa) significantly suppressed and that reduction of Distal-less enhanced the DREF-induced rough eye phenotype. The results suggest a possibility that DREF activity might be regulated by protein complexes that play a role in modulating chromatin structure. Genetic crosses of transgenic flies expressing DREF to a collection of Drosophila deficiency stocks allowed us to identify several genomic regions, deletions of which caused enhancement or suppression of the DREF-induced rough eye phenotype. These deletions should be useful to identify novel targets of DREF and its positive or negative regulators.

Animals↗
PubMed2005

DREF is required for efficient growth and cell cycle progression in Drosophila imaginal discs.

Based on overexpression studies and target gene analyses, the transcription factor DNA replication-related element factor (DREF) has been proposed to regulate growth and replication in Drosophila melanogaster. Here we present loss-of-function experiments to analyze the contribution of DREF to these processes. RNA interference-mediated extinction of DREF function in vivo demonstrates a requirement for the protein for normal progression through the cell cycle and consequently for growth of imaginal discs and the derived adult organs. We show that DREF regulates the expression of genes that are required for the transition of imaginal disc cells through S phase. In conditions of suppressed apoptosis, DREF activation can cause overgrowth of developing organs. These data establish DREF as a global regulator of transcriptional programs that mediate cell proliferation and organ growth during animal development.

Animals↗
PubMed2002

Analogy in moral deliberation: the role of imagination and theory in ethics.

This paper develops themes addressed in an article by Eric Wiland in the Journal of Medical Ethics 2000;26:466-8, where he aims to contribute to the debate concerning the moral status of abortion, and to emphasise the importance of analogies in moral argument. In the present paper I try to secure more firmly a novel understanding of why analogy is an essential component in the attempt to justify moral beliefs. I seek to show how analogical argument both encapsulates and exercises the notions of rationality and imagination and that the construction, development, and comparison of analogies fundamentally underpins ethical argument. In so doing, it enables us to adopt imaginative and ethically illuminating perspectives but in a manner that does not relinquish any claims to intellectual rigour. I present a critique of a brand of "moral particularism" by showing how it cannot, if construed in a certain way, adequately conceive of how we use analogies and imaginary cases in ethics. Although such a particularism is thus impotent with regard to ethical debate, I show that the wider motivation behind particularism that can be extracted is of clear relevance and importance to medical practitioners.

Abortion, Induced↗
PubMed1995

Taped imaginal exposure as a treatment for post-traumatic stress reactions.

The efficacy of taped imaginal exposure as a treatment for Post-Traumatic Stress Reactions (PTSR) was assessed in eighteen consecutive outpatients, including Gulf War veterans. Detailed present-tense scripts of their personal traumatic experiences were prepared and in all but two cases audio-taped and listened to regularly. The severity of PTSR and standard questionnaire scores (including the IES, BDI, GHQ8 and the SCL 90) all showed statistically significant improvements post treatment and at three month follow-up. This case series confirms the potential efficacy of taped imaginal exposure in the treatment of full and partial forms of Post-Traumatic Stress Disorder (PTSD). The simplicity of its administration and acceptability to the individual suggest that it is worthy of more thorough research.

Adult↗
PubMed1991

Statistical analysis for single-case designs. Evaluating outcome of imaginal exposure treatment of chronic PTSD.

A recently developed statistical method for single-case subject designs based on classical test theory was used to examine the efficacy of imaginal exposure treatment for posttraumatic stress disorder (PTSD) in four Vietnam veterans. The method was sensitive to intraindividual changes across different outcome measures even when relatively few data points were available. Two veterans clearly improved from exposure and maintained their gains at 3- and 15-month follow-ups. One veteran improved marginally, whereas one veteran's symptoms worsened. Changes in heart rate monitored over the first two imaginal exposures indicated that veterans with greater heart-rate habituation responded better to exposure than did veterans with less or no habituation. The results suggest that the statistical method illustrated here has some advantages over other methods (e.g., visual inspection, time-series analysis) for examining clinical interventions in single-case designs.

Adult↗
PubMed2002

Loss of the imagined past: an emotional obstacle to medical compliance in kidney transplant recipients.

Among kidney transplant recipients, the concepts of grief and bereavement have been considered in terms of graft rejection, side effects of drugs, or death of the donor. However, our research suggests that even after a successful kidney transplantation, patients may present with feelings of bereavement, grief, or low mood, which may appear paradoxical because they have just received a much desired transplant. This sense of bereavement should be considered in terms of an imagined past, which may help to understand the patient's current mood changes and medical noncompliance. In the case report presented here, we have used the concept of systemic integrative psychotherapy to analyze change in a patient's life. Based on our research, we suggest that feelings of bereavement and grief are generated as patients come to terms with their past, which has been irretrievably lost to chronic illness, and contemplate their future. Feelings of grief and bereavement in the posttransplant period may be due to the loss of an imagined past, and must be differentiated from the bereavement the patient feels for the donor and the donor family. These feeling of loss, if not resolved, may lead to social isolation and medical noncompliance.

Activities of Daily Living↗
PubMed1978

The effects of mood upon imaginal thought.

The effects of mood upon imaginal thought were explored with a highly trained undergraduate female hypnotic subject. She was hypnotically programmed to experience free-floating anxiety or pleasure in varying degrees just before the exposure of combinations of three Blacky Pictures, and to produce dreamlike imagery in response to the Blacky stimuli while under sway of the mood. Data from 98 dream trials, separated by amnesia, indicated that the affective states clearly influenced imaginal processes. Blind ratings by a psychoanalyst showed the anxiety moods to be more closely associated with primary-process features characteristic of nocturnal dreams, whereas pleasure had a relatively higher incidence of daydreamlike ratings. Empirical analysis of themes yielded significant relationships of anxiety to physical injury to the self and verbal aggression toward others; pleasure was associated with circular movements and overt sex themes.

Journal Article↗
PubMed2000

Functional MRI correlates of real and imagined tool-use pantomimes.

OBJECTIVE: To study the pattern of cerebral activation related to the performance of tool-use pantomimes with functional MRI (fMRI) using a task-subtraction design. BACKGROUND: Tool use comprises a particular category of transitive actions. Inability to pantomime the use of tools has been classically associated with retrorolandic dominant hemisphere damage. However, where in the left hemisphere these transitive representations are generated is unclear. METHODS: Echoplanar images were acquired in eight alternating task and control periods. Sixteen right-handed normal adults pantomimed the use of common tools and utensils with each hand. The control condition consisted of a sequence of nonsymbolic complex movements of forearm, hand, and fingers at a self-paced rate. Eight individuals also imagined the execution of the real task and control actions. A repeated measures ANOVA compared activations in five regions of interest in each hemisphere. RESULTS: Regardless of which hand was used, the left hemisphere was more active than the right in both real (p < 0.02) and imagined (p < 0.04) tasks. Activations clustered in the left intraparietal cortex and posterior dorsolateral frontal cortex. CONCLUSIONS: Pantomiming the use of tools is associated with activation of the left intraparietal cortex and dorsolateral frontal cortex. The left intraparietal cortex may store the representations of tool-use formulae, whereas the dorsolateral frontal cortex activation may reflect the switching between innervatory motor programs.

Adolescent↗
PubMed2002

Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila.

During animal development, organ size is determined primarily by the amount of cell proliferation, which must be tightly regulated to ensure the generation of properly proportioned organs. However, little is known about the molecular pathways that direct cells to stop proliferating when an organ has attained its proper size. We have identified mutations in a novel gene, shar-pei, that is required for proper termination of cell proliferation during Drosophila imaginal disc development. Clones of shar-pei mutant cells in imaginal discs produce enlarged tissues containing more cells of normal size. We show that this phenotype is the result of both increased cell proliferation and reduced apoptosis. Hence, shar-pei restricts cell proliferation and promotes apoptosis. By contrast, shar-pei is not required for cell differentiation and pattern formation of adult tissue. Shar-pei is also not required for cell cycle exit during terminal differentiation, indicating that the mechanisms directing cell proliferation arrest during organ growth are distinct from those directing cell cycle exit during terminal differentiation. shar-pei encodes a WW-domain-containing protein that has homologs in worms, mice and humans, suggesting that mechanisms of organ growth control are evolutionarily conserved.

Amino Acid Sequence↗
PubMed2005

Developmental analysis and squamous morphogenesis of the peripodial epithelium in Drosophila imaginal discs.

Imaginal discs of Drosophila provide an excellent system with which to study morphogenesis, pattern formation and cell proliferation in an epithelium. Discs are sac-like in structure and are composed of two epithelial layers: an upper peripodial epithelium and lower disc proper. Although development of the disc proper has been studied extensively in terms of cell proliferation, cell signaling mechanisms and pattern formation, little is known about these same processes in the peripodial epithelium. We address this topic by focusing on morphogenesis, compartmental organization, proliferation and cell lineage of the PE in wing, second thoracic leg (T2) and eye discs. We show that a subset of peripodial cells in different imaginal discs undergo a cuboidal-to-squamous cell shape change at distinct larval stages. We find that this shape change requires both Hedgehog and Decapentapelagic, but not Wingless, signaling. Additionally, squamous morphogenesis shifts the anteroposterior (AP) compartment boundary in the peripodial epithelium relative to the stationary AP boundary in the disc proper. Finally, by lineage tracing cells in the PE, we surprisingly find that peripodial cells are displaced into the disc proper during larval development and this movement leads to Ubx repression.

Animals↗
PubMed2005

Arrow (LRP6) and Frizzled2 cooperate to degrade Wingless in Drosophila imaginal discs.

Lysosome-mediated ligand degradation is known to shape morphogen gradients and modulate the activity of various signalling pathways. We have investigated the degradation of Wingless, a Drosophila member of the Wnt family of secreted growth factors. We find that one of its signalling receptors, Frizzled2, stimulates Wingless internalization both in wing imaginal discs and cultured cells. However, this is not sufficient for degradation. Indeed, as shown previously, overexpression of Frizzled2 leads to Wingless stabilization in wing imaginal discs. We show that Arrow (the Drosophila homologue of LRP5/6), another receptor involved in signal transduction, abrogates such stabilization. We provide evidence that Arrow stimulates the targeting of Frizzled2-Wingless (but not Dally-like-Wingless) complexes to a degradative compartment. Thus, Frizzled2 alone cannot lead Wingless all the way from the plasma membrane to a degradative compartment. Overall, Frizzled2 achieves ligand capture and internalization, whereas Arrow, and perhaps downstream signalling, are essential for lysosomal targeting.

Animals↗
PubMed1987

Fate map of the eye-antennal imaginal disc of the tumorous-head mutant of Drosophila melanogaster.

In specific genetic backgrounds, a mutation in the tuh-3 gene results in the homeotic transformation of head structures to either leg disc derivatives or structures normally found in the extreme posterior end of wild-type animals. The origins of the homeotic structures were mapped to defined positions in the eye-antennal imaginal disc by transplanting abnormal regions of discs isolated from tuh-3 mutants into host mwh;e4 larvae. These metamorphosed implants were removed and differentiated structures were identified. Of 211 successfully recovered implants, 157 gave rise to homeotic tissue: abdominal tergite, male or female external genitalia and/or leg tissue. Transformations to abdominal tergite occurred primarily in cells taken from the eye region of the compound disc. Male and female genitalia arose most often in implants taken from the antennal portion of the disc, although some tissue taken from the lateral region of the eye disc also gave rise to external genitalia. Leg structures came exclusively from implants from the antennal region of the imaginal disc. These results suggest that cells from within specific regions of the eye-antennal compound disc are constrained in their developmental potential. An obvious constraint observed with this mutation is a dorsal/ventral one: Cells from the eye disc, a dorsal structure, primarily gave rise to other dorsal structures, abdominal tergite tissue. Cells from the antennal disc, a ventrally derived structure, primarily gave rise to other ventral structures including genital tissue and distal leg.

Animals↗
PubMed1988

Ectopic expression of homeotic genes caused by the elimination of the Polycomb gene in Drosophila imaginal epidermis.

The morphological patterns in the adult cuticle of Drosophila are determined principally by the homeotic genes of the bithorax and Antennapedia complexes. We find that many of these genes become indiscriminately active in the adult epidermis when the Pc gene is eliminated. By using the Pc3 mutation and various BX-C mutant combinations, we have generated clones of imaginal cells possessing different combinations of active homeotic genes. We find that, in the absence of BX-C genes, Pc- clones develop prothoracic patterns; this is probably due to the activity of Sex combs reduced which overrules Antennapedia. Adding contributions of Ultrabithorax, abdominal-A and Abdominal-B results in thoracic or abdominal patterns. We have established a hierarchical order among these genes: Antp less than Scr less than Ubx less than abd-A less than Abd-B. In addition, we show that the engrailed gene is ectopically active in Pc- imaginal cells.

Animals↗
PubMed1989

Imaginal disc-autonomous expression of a defect in sensory bristle patterning caused by the lethal(3)ecdysoneless1 (1(3)ecd1) mutation of Drosophila melanogaster.

The temperature-sensitive mutation 1(3)ecd1 of Drosophila melanogaster is known to autonomously impair the ability of the larval prothoracic gland to produce the steroid molting hormone ecdysone in response to stimulation by the tropic neuropeptide prothoracicotropic hormone. It is shown that autonomous expression of the 1(3)ecd1 mutation in metamorphosing imaginal tissues disrupts the spatial pattern of sensory bristles. Transfer of homozygous mutant animals to the restrictive temperature at the time of pupariation resulted in the elimination of sensory microchaetae and macrochaetae. This effect was specific to the sensory bristles; nonsensory bristles were not eliminated, nor were other types of innervated cuticular sense organs. In the case of the dorsal thoracic macrochaetae, normal ecd gene function is required during an early period of bristle development (0-18 h after puparium formation at 20 degrees C). It is during this period that important determinative events take place in developing imaginal tissues that are responsible for the establishment of bristle progenitor cells. It is proposed that the ecd gene product may be required for the response of certain classes of cells to specific, regulatory signals.

Animals↗
PubMed1990

Ecdysone-dependent proteolysis of an apical surface glycoprotein may play a role in imaginal disc morphogenesis in Drosophila.

An apical surface glycoprotein, designated gp125 for its apparent molecular weight of 125,000, appears in Ca2(+)-free, ionic detergent extracts of imaginal discs of Drosophila melanogaster in response to the steroid hormone, 20-hydroxyecdysone (20-HE). Gp125 is not synthesized in response to 20-HE, but results from modification of an existing macromolecule. Treatment of discs or larval epidermis with serine protease (e.g., trypsin) results in hormone-independent production of gp125. Antiserum raised to electrophoretically purified gp125 recognizes, in addition to gp125, two closely related glycoproteins with higher apparent molecular weights, gp200 and gp180. This family of glycoproteins is localized at the apical surface of imaginal disc cells and of the epidermal epithelium in embryos, larvae and prepupae. Ca2+ affects both the solubility and the proteolytic products of this family of glycoproteins. We discuss the possibility that gp125 is generated through the action of a hormonally controlled serine protease in a process that is necessary for disc morphogenesis.

Animals↗