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L M Nagy

Publications and source records attributed to L M Nagy.

At least 19 recordsLinked to original sources
PubMed2002

A complex role for distal-less in crustacean appendage development.

The developing leg of Drosophila is initially patterned by subdivision of the leg into proximal and distal domains by the activity of the homeodomain proteins Extradenticle (Exd) and Distal-less (Dll). These early domains of gene expression are postulated to reflect a scenario of limb evolution in which an undifferentiated appendage outgrowth was subdivided into two functional parts, the coxapodite and telopodite. The legs of most arthropods have a more complex morphology than the simple rod-shaped leg of Drosophila. We document the expression of Dll and Exd in two crustacean species with complex branched limbs. We show that in these highly modified limbs there is a Dll domain exclusive of Exd but there is also extensive overlap in Exd and Dll expression. While arthropod limbs all appear to have distinct proximal and distal domains, those domains do not define homologous structures throughout arthropods. In addition, we find a striking correlation throughout the proximal/distal extent of the leg between setal-forming cells and Dll expression. We postulate that this may reflect a pleisiomorphic function of Dll in development of the peripheral nervous system. In addition, our results confirm previous observations that branch formation in multiramous arthropod limbs is not regulated by a simple iteration of the proximal/distal patterning module employed in Drosophila limb development.

Animals↗
PubMed2001

Developmental modularity and the evolutionary diversification of arthropod limbs.

Segmentation is one of the most salient characteristics of arthropods, and differentiation of segments along the body axis is the basis of arthropod diversification. This article evaluates whether the evolution of segmentation involves the differentiation of already independent units, i.e., do segments evolve as modules? Because arthropod segmental differentiation is commonly equated with differential character of appendages, we analyze appendages by comparing similarities and differences in their development. The comparison of arthropod limbs, even between species, is a comparison of serially repeated structures. Arthropod limbs are not only reiterated along the body axis, but limbs themselves can be viewed as being composed of reiterated parts. The interpretation of such reiterated structures from an evolutionary viewpoint is far from obvious. One common view is that serial repetition is evidence of a modular organization, i.e., repeated structures with a common fundamental identity that develop semi-autonomously and are free to diversify independently. In this article, we evaluate arthropod limbs from a developmental perspective and ask: are all arthropod limbs patterned using a similar set of mechanisms which would reflect that they all share a generic coordinate patterning system? Using Drosophila as a basis for comparison, we find that appendage primordia, positioned along the body using segmental patterning coordinates, do indeed have elements of common identity. However, we do not find evidence of a single coordinate system shared either between limbs or among limb branches. Data concerning the other diagnostic of developmental modularity--semi-autonomy of development--are not currently available for sufficient taxa. Nonetheless, some data comparing patterns of morphogenesis provide evidence that limbs cannot always be temporally or spatially decoupled from the development of their neighbors, suggesting that segment modularity is a derived character.

Adaptation, Physiological↗
PubMed2001

MAPK signaling by the D quadrant embryonic organizer of the mollusc Ilyanassa obsoleta.

Classical experiments performed on the embryo of the mollusc Ilyanassa obsoleta demonstrate that the 3D macromere acts as an embryonic organizer, by signaling to other cells and inducing them to assume the correct pattern of cell fates. We have discovered that MAP kinase signaling is activated in the cells that require the signal from 3D for normal differentiation. Preventing specification of the D quadrant lineage by removing the polar lobe disrupts the pattern of MAPK activation, as does ablation of the 3D macromere itself. Blocking MAPK activation with the MAP Kinase inhibitor U0126 produces larvae that differentiate the same limited complement of tissues as D quadrant deletions. Our results suggest that the MAP Kinase signaling cascade transduces the inductive signal from 3D and specifies cell fate among the cells that receive the signal.

Animals↗
PubMed2000

Leg development in flies versus grasshoppers: differences in dpp expression do not lead to differences in the expression of downstream components of the leg patterning pathway.

All insect legs are structurally similar, characterized by five primary segments. However, this final form is achieved in different ways. Primitively, the legs developed as direct outgrowths of the body wall, a condition retained in most insect species. In some groups, including the lineage containing the genus Drosophila, legs develop indirectly from imaginal discs. Our understanding of the molecular mechanisms regulating leg development is based largely on analysis of this derived mode of leg development in the species D. melanogaster. The current model for Drosophila leg development is divided into two phases, embryonic allocation and imaginal disc patterning, which are distinguished by interactions among the genes wingless (wg), decapentaplegic (dpp) and distalless (dll). In the allocation phase, dll is activated by wg but repressed by dpp. During imaginal disc patterning, dpp and wg cooperatively activate dll and also indirectly inhibit the nuclear localization of Extradenticle (Exd), which divide the leg into distal and proximal domains. In the grasshopper Schistocerca americana, the early expression pattern of dpp differs radically from the Drosophila pattern, suggesting that the genetic interactions that allocate the leg differ between the two species. Despite early differences in dpp expression, wg, Dll and Exd are expressed in similar patterns throughout the development of grasshopper and fly legs, suggesting that some aspects of proximodistal (P/D) patterning are evolutionarily conserved. We also detect differences in later dpp expression, which suggests that dpp likely plays a role in limb segmentation in Schistocerca, but not in Drosophila. The divergence in dpp expression is surprising given that all other comparative data on gene expression during insect leg development indicate that the molecular pathways regulating this process are conserved. However, it is consistent with the early divergence in developmental mode between fly and grasshopper limbs.

Animals↗
PubMed1999

The role of wingless in the development of multibranched crustacean limbs.

Arthropods are the most diverse and speciose group of organisms on earth. A key feature in their successful radiation is the ease with which various appendages become readily adapted to new functions in novel environments. Arthropod limbs differ radically in form and function, from unbranched walking legs to multibranched swimming paddles. To uncover the developmental and genetic mechanisms underlying this diversification in form, we ask whether a three-signal model of limb growth based on Drosophila experiments is used in the development of arthropod limbs with variant shape. We cloned a Wnt-1 ortholog (Tlwnt-1) from Triops longicaudatus, a basal crustacean with a multibranched limb. We examined the mRNA in situ hybridization pattern during larval development to determine whether changes in wg expression are correlated with innovation in limb form. During larval growth and segmentation Tlwnt-1 is expressed in a segmentally reiterated pattern in the trunk. Unexpectedly, this pattern is restricted to the ventral portion of the epidermis. During early limb formation the single continuous stripe of Tlwnt-1 expression in each segment becomes ventrolaterally restricted into a series of shorter stripes. Some but not all of these shorter stripes correspond to what becomes the ventral side of a developing limb branch. We conclude that the Drosophila model of limb development cannot explain all types of arthropod proximodistal outgrowths, and that the multibranched limb of Triops develops from an early reorganization of the ventral body wall. In Triops, Tlwnt-1 plays a semiconservative role similar to that played by Drosophila wingless in segmentation and limb formation, and morphological innovation in limb form arises in part through an early modulation in the expression of the Tlwnt-1 gene.

Amino Acid Sequence↗
PubMed1998

Development of polyembryonic insects: a major departure from typical insect embryogenesis.

The parasitic wasp Copidosoma floridanum represents the most extreme form of polyembryonic development known, forming up to 2000 embryos from a single egg. To understand the mechanisms of embryonic patterning in polyembryonic wasps and the evolutionary changes that led to this form of development we have analyzed embryonic development at the cellular level using confocal and scanning electron microscopy. C. floridanum embryogenesis can be divided into three phases: (1) early cleavage that leads to formation of a primary morula, (2) a proliferative phase that involves partitioning of embryonic cells into thousands of morulae, and (3) morphogenesis whereby individual embryos develop into larvae. This developmental program represents a major departure from typical insect embryogenesis, and we describe several features of morphogenesis unusual for insects. The early development of polyembryonic wasps, which likely evolved in association with a shift in life history to endoparasitism, shows several analogies with mammalian embryogenesis, including early separation of extraembryonic and embryonic cell lineages, formation of a morula and embryonic compaction. However, the late morphogenesis of polyembryonic wasps proceeds in a fashion conserved in all insects. Collectively, this suggests a lack of developmental constraints in early development, but a strong conservation of the phylotypic stage.

Animals↗
PubMed1997

Noradrenergic and serotonergic function in posttraumatic stress disorder.

BACKGROUND: Yohimbine hydrochloride produces marked behavioral and cardiovascular effects in combat veterans with posttraumatic stress disorder (PTSD). In the present study, yohimbine was used as a probe of noradrenergic activity, and meta-chlorophenylpiperazine (m-CPP) as a probe of serotonergic activity. To our knowledge, this is the first study to describe the behavioral and cardiovascular effects of meta-CPP in patients with PTSD, and to compare these effects with those of yohimbine. METHOD: Twenty-six patients with PTSD and 14 healthy subjects each received an intravenous infusion of yohimbine hydrochloride (0.4 mg/kg), m-CPP (1.0 mg/kg), or saline solution on 3 separate test days in a randomized balanced order and in double-blind fashion. Behavioral and cardiovascular measurements were determined at multiple times. RESULTS: Eleven (42%) of the patients with PTSD experienced yohimbine-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, but not in cardiovascular measurements. Eight patients (31%) with PTSD experienced m-CPP-induced panic attacks and had significantly greater increases compared with controls in anxiety, panic, and PTSD symptoms, and in standing diastolic blood pressure. Yohimbine-induced panic attacks tended to occur in different patients from m-CPP-induced panic attacks. CONCLUSION: These data suggest the presence of 2 neurobiological subgroups of patients with PTSD, one with a sensitized noradrenergic system, and the other with a sensitized serotonergic system.

Adult↗
PubMed1996

Polyembryonic development: insect pattern formation in a cellularized environment.

THe polyembryonic wasp Copidosoma floridanum produces up to 2000 individuals from a single egg. During the production of individual embryos the original anteroposterior axis of the egg is lost and axial patterning must subsequently be reestablished within each embryo. The mechanism by which this occurs is unknown. In most insects, egg polarity is established during oogenesis and early development takes place in a syncytium. In Drosophila melanogaster, the syncytium is considered essential for establishing the morphogenetic gradients that initiate segmental patterning. However, we found that development of C. floridanum occurs almost exclusively in a cellularized environment. To determine whether the D. melanogaster patterning cascade is conserved in the absence of a syncytium, we analyzed the expression of Even-skipped, Engrailed and Ultrabithorax/Abdominal-A during polyembryonic development. Here we show that in spite of the absence of a syncytium, the elements of the D. melanogaster segmentation hierarchy are conserved. The segment-polarity gene Engrailed and the homeotic genes Ultrabithorax/Abdominal-A are expressed in a conserved pattern relative to D. melanogaster. However, we detect an alteration in the expression of the Even-skipped antigen. Even-skipped is initially expressed in segmentally reiterated stripes and not in the pair-rule pattern as it is in D. melanogaster. We also observe that the expression of these regulatory proteins does not occur during the early proliferative phases of polyembryony. Our results indicate that a syncytium is not required for segmental patterning in this insect.

Animals↗
PubMed1995

Effects of the benzodiazepine antagonist flumazenil in PTSD.

OBJECTIVE: Evidence from preclinical and clinical studies suggests a role for alterations in the benzodiazepine/GABAA receptor complex in stress and anxiety. Flumazenil is a relatively pure benzodiazepine/GABAA antagonist with limited intrinsic activity. In panic disorder patients, but not healthy controls, flumazenil has been demonstrated to provoke panic attacks. METHOD: Vietnam combat veterans with PTSD (n = 14) received 90-second intravenous infusions of flumazenil 2 mg or placebo in a double-blind, crossover study design. PTSD symptomology was assessed using the PTSD Symptom Scale, and anxiety symptoms were measured with visual analogue rating scales. RESULTS: There was no significant difference in PTSD and anxiety symptoms between administration of flumazenil and placebo. CONCLUSION: Flumazenil administration does not produce an increase in anxiety and PTSD symptoms in patients with PTSD. This suggests that PTSD and panic disorder are dissimilar in terms of benzodiazepine/GABAA system function.

Anxiety Disorders↗
PubMed1995

The development of a Clinician-Administered PTSD Scale.

Several interviews are available for assessing PTSD. These interviews vary in merit when compared on stringent psychometric and utility standards. Of all the interviews, the Clinician-Administered PTSD Scale (CAPS-1) appears to satisfy these standards most uniformly. The CAPS-1 is a structured interview for assessing core and associated symptoms of PTSD. It assesses the frequency and intensity of each symptom using standard prompt questions and explicit, behaviorally-anchored rating scales. The CAPS-1 yields both continuous and dichotomous scores for current and lifetime PTSD symptoms. Intended for use by experienced clinicians, it also can be administered by appropriately trained paraprofessionals. Data from a large scale psychometric study of the CAPS-1 have provided impressive evidence of its reliability and validity as a PTSD interview.

Humans↗
PubMed1995

Yohimbine facilitated acoustic startle in combat veterans with post-traumatic stress disorder.

Preclinical and clinical studies have suggested that the acoustic startle reflex (ASR) is a useful model to investigate the neurochemical basis of anxiety and fear states. This work has revealed that the anxiogenic alpha-2 receptor antagonist, yohimbine, increases the amplitude of the ASR in laboratory animals and in healthy human controls. Because of the growing body of data that support the hypothesis that severe stress results in substantial alterations in noradrenergic neuronal reactivity, the present investigation evaluated the effects of yohimbine on the ASR of 18 patients with PTSD and 11 healthy combat controls. Subjects received IV yohimbine (0.4 mg/kg) or saline placebo on 2 separate days in a randomized double blind placebo control design. A trial of two tone frequencies with varied intensity (90, 96, 102, 108, 114 dB) white noise and instantaneous rise time, was delivered binaurally through headphones. Tones were delivered every 25-60 s, for a 40-ms duration. Startle testing was performed 80 min post-infusion and lasted 15-20 min. Yohimbine significantly increased the amplitude, magnitude and probability of the ASR in combat veterans with PTSD, but did not do so in combat controls. Overall startle was significantly larger in the PTSD subjects; however, this did not account for the differential effect of yohimbine, since yohimbine had no significant effect in the control group. This study demonstrates an excitatory effect of yohimbine on the amplitude, magnitude and probability of the ASR in PTSD patients that is not seen in combat controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Trauma-related symptoms in veterans of Operation Desert Storm: a 2-year follow-up.

OBJECTIVE: This study was a 2-year follow-up in an ongoing prospective examination of development of trauma-related symptoms over time in a community group of veterans of Operation Desert Storm. METHOD: Sixty-two National Guard reservists, from one medical and one military police unit, completed the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder and a DSM-III-R-based posttraumatic stress disorder (PTSD) symptom scale 1 month, 6 months, and 2 years after returning from the Middle East. Differences in symptom severity over time were analyzed by using repeated measure analyses of variance. RESULTS: Scores on the Mississippi scale, but not the DSM-III-R PTSD scale, increased significantly over time. Symptoms of hyperarousal were more severe at all time points than were symptoms of reexperiencing or avoidance. Level of combat exposure, as reflected by the Desert Storm trauma questionnaire, was significantly associated with the score on the Mississippi scale at 2 years but not at 1 month or 6 months. All subjects who met the Mississippi scale's diagnostic criteria for PTSD at 1 or 6 months still met the criteria at 2 years. CONCLUSIONS: Although symptoms were relatively mild, there was an overall increase in PTSD symptoms over 2 years. The statistical relationship between level of combat exposure and PTSD symptoms at 2 years, and not before, suggests that it may take time for the consequences of traumatic exposure to become apparent. Moreover, degree of exposure may be important in predicting the eventual development of symptoms. Continued follow-up will address the evolution of PTSD symptoms in Gulf War veterans.

Female↗
PubMed1995

Premorbid onset of psychopathology in long-term recovered anorexia nervosa.

It is recognized that patients with anorexia nervosa commonly have other psychiatric illnesses. No study, to our knowledge, has determined whether these other psychiatric disorders occur prior to the age of onset of anorexia nervosa. We obtained a retrospective history from 24 subjects who were long term (more than 1 year) recovered from anorexia nervosa. We found that 58% reported that they had the onset of one or more childhood anxiety disorder diagnoses at the age of 10 +/- 5 years old. This was 5 years before the mean age of onset of anorexia nervosa. The onset of depression was about 1 year before the onset of anorexia nervosa in about one half the subjects. Alcohol and substance abuse/dependency tended to occur after the onset of anorexia nervosa and only occurred in anorexic subjects who binged and/or purged. The early and common onset of childhood anxiety disorders in a substantial percentage of anorexics raises the possibility that childhood anxiety disorders herald the first behavioral expression of a biologic vulnerability in some subjects who develop anorexia nervosa.

Adult↗
PubMed1994

Insect segmentation. A glance posterior.

Segmentation gene expression patterns can be radically different in some short-germ and long-germ insects, but other types of short/intermediate-germ insects may use Drosophila-like segmentation mechanisms.

Animals↗
PubMed1994

Conservation of wingless patterning functions in the short-germ embryos of Tribolium castaneum.

During embryogenesis, all insects reach a conserved, or phylotypic, stage at which all future segments are present. Different insects, however, arrive at this stage by overtly different pathways. In the long-germ insect Drosophila melanogaster, segmentation of the entire embryo occurs nearly simultaneously and results from the action of a cascade of transcriptional regulatory factors that operate in the acellular environment of the syncytial blastoderm. In short-germ insects, segmentation occurs in an anterior-to-posterior sequence, within a cellular environment, and might then be dependent on intercellular signalling. To compare the molecular mechanisms of segmentation, we have isolated a homologue of the Drosophila wingless gene, a mediator of cell-cell communications, from the short-germ beetle Tribolium castaneum. The principal features of wingless expression patterns in Drosophila are conserved in Tribolium, including its early deployment in rostral and caudal domains in the blastoderm, its segmental iteration in cells immediately anterior to cells expressing the engrailed gene, and its later restriction to a ventral sector of the developing appendages.

Amino Acid Sequence↗