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Biomedical subjects

S Carroll

Publications and source records attributed to S Carroll.

At least 19 recordsLinked to original sources
PubMed1999

Ultrabithorax function in butterfly wings and the evolution of insect wing patterns.

BACKGROUND: . The morphological and functional evolution of appendages has played a critical role in animal evolution, but the developmental genetic mechanisms underlying appendage diversity are not understood. Given that homologous appendage development is controlled by the same Hox gene in different organisms, and that Hox genes are transcription factors, diversity may evolve from changes in the regulation of Hox target genes. Two impediments to understanding the role of Hox genes in morphological evolution have been the limited number of organisms in which Hox gene function can be studied and the paucity of known Hox-regulated target genes. We have therefore analyzed a butterfly homeotic mutant 'Hindsight', in which portions of the ventral hindwing pattern are transformed to ventral forewing identity, and we have compared the regulation of target genes by the Ultrabithorax (Ubx) gene product in Lepidopteran and Dipteran hindwings. RESULTS: . We show that Ubx gene expression is lost from patches of cells in developing Hindsight hindwings, correlating with changes in wing pigmentation, color pattern elements, and scale morphology. We use this mutant to study how regulation of target genes by Ubx protein differs between species. We find that several Ubx-regulated genes in the Drosophila haltere are not repressed by Ubx in butterfly hindwings, but that Distal-less (Dll) expression is regulated by Ubx in a unique manner in butterflies. CONCLUSIONS: . The morphological diversification of insect hindwings has involved the acquisition of different sets of target genes by Ubx in different lineages. Changes in Hox-regulated target gene sets are, in general, likely to underlie the morphological divergence of homologous structures between animals.

Animals↗
PubMed1999

Falls among healthy, community-dwelling, older women: a prospective study of frequency, circumstances, consequences and prediction accuracy.

OBJECTIVE: Most studies of falls among older people have focused on those with some degree of balance or mobility impairment. This study aimed to establish whether falls and associated injuries were a major problem among healthy, older women, whether there were some common features in the falls, and whether these falls could be accurately predicted. METHOD: Ninety-six healthy, active community-dwelling women in Melbourne, Australia, aged at least 70 years (mean 74.1 +/- 4.0) were initially measured on a comprehensive series of laboratory and clinical balance tests, gait, strength and psychometric measures. Subjects were monitored for falls events, circumstances and consequences by use of falls diaries and monthly phone calls. Baseline measures of clinical balance measures and gait were comparable to other studies reporting scores on these measures in samples of healthy older people. RESULTS: During the 12-month follow-up period, 49% of subjects fell, with 23% falling more than once; 9% suffered fractures as a result of their fall and 10% suffered strains or other moderate injuries. Many of the falls occurred during non-threatening activities such as walking, often under altered sensory or environmental conditions. Multivariate logistic regression identified gait symmetry and gait double support duration as the variables most strongly associated with prediction of multiple fallers. CONCLUSIONS: The results highlight that falls are a major problem among healthy active older women, and that targeted falls prevention programs are required for this group.

Accidental Falls↗
PubMed1999

Prolonged contraction-relaxation cycle of fast-twitch muscles in parvalbumin knockout mice.

The calcium-binding protein parvalbumin (PV) occurs at high concentrations in fast-contracting vertebrate muscle fibers. Its putative role in facilitating the rapid relaxation of mammalian fast-twitch muscle fibers by acting as a temporary buffer for Ca2+ is still controversial. We generated knockout mice for PV (PV -/-) and compared the Ca2+ transients and the dynamics of contraction of their muscles with those from heterozygous (PV +/-) and wild-type (WT) mice. In the muscles of PV-deficient mice, the decay of intracellular Ca2+ concentration ([Ca2+]i) after 20-ms stimulation was slower compared with WT mice and led to a prolongation of the time required to attain peak twitch tension and to an extension of the half-relaxation time. The integral [Ca2+]i in muscle fibers of PV -/- mice was higher and consequently the force generated during a single twitch was approximately 40% greater than in PV +/- and WT animals. Acceleration of the contraction-relaxation cycle of fast-twitch muscle fibers by PV may confer an advantage in the performance of rapid, phasic movements.

Animals↗
PubMed1998

The Vestigial and Scalloped proteins act together to directly regulate wing-specific gene expression in Drosophila.

A small number of major regulatory (selector) genes have been identified in animals that control the development of particular organs or complex structures. In Drosophila, the vestigial gene is required for wing formation and is able to induce wing-like outgrowths on other structures. However, the molecular function of the nuclear Vestigial protein, which bears no informative similarities to other proteins, was unknown. Here, we show that Vestigial requires the function of the Scalloped protein, a member of the TEA family of transcriptional regulators, to directly activate the expression of genes involved in wing morphogenesis. Genetic and molecular analyses reveal that Vestigial regulates wing identity by forming a complex with the Scalloped protein that binds sequence specifically to essential sites in wing-specific enhancers. These enhancers also require the direct inputs of signaling pathways, and the response of an enhancer can be switched to another pathway through changes in signal-transducer binding sites. Combinatorial regulation by selector proteins and signal transducers is likely to be a general feature of the tissue-specific control of gene expression during organogenesis.

Animals↗
PubMed1998

Ultrabithorax regulates genes at several levels of the wing-patterning hierarchy to shape the development of the Drosophila haltere.

Arthropods and vertebrates are constructed of many serially homologous structures whose individual patterns are regulated by Hox genes. The Hox-regulated target genes and developmental pathways that determine the morphological differences between any homologous structures are not known. The differentiation of the Drosophila haltere from the wing through the action of the Ultrabithorax (Ubx) gene is a classic example of Hox regulation of serial homology, although no Ubx-regulated genes in the haltere have been identified previously. Here, we show that Ubx represses the expression of the Wingless (Wg) signaling protein and a subset of Wg- and Decapentaplegic-activated genes such as spalt-related, vestigial, Serum Response Factor, and achaete-scute, whose products regulate morphological features that differ between the wing and haltere. In addition, we found that some genes in the same developmental pathway are independently regulated by Ubx. Our results suggest that Ubx, and Hox genes in general, independently and selectively regulate genes that act at many levels of regulatory hierarchies to shape the differential development of serially homologous structures.

Animals↗
PubMed1998

Diurnal variation of adrenocortical activity in chronic fatigue syndrome.

Baseline morning and evening serum cortisol and ACTH concentrations, and diurnal changes in hormone levels, were measured in 30 patients with chronic fatigue syndrome (CFS) but without concurrent depressive disorder and a control group of 15 weight-, age- and sex-matched healthy volunteers. Morning cortisol levels were non-significantly lower in CFS patients, while evening levels were non-significantly higher. ACTH concentrations were non-significantly higher in both the morning and evening. The diurnal change in cortisol levels was significantly less in CFS than in controls (p < 0.05). In CFS subjects, evening levels of cortisol correlated significantly with measures of general health and physical functioning, while diurnal change in cortisol was positively correlated with measures of functional improvement over the past year and current social functioning. These results suggest that there is a relationship between adrenocortical function and disability in CFS, but do not reveal the causal connection.

Adrenal Cortex↗
PubMed1998

Breast cancer. Part 3: Psychosocial care.

Psychosocial care, information-giving and issues surrounding patient choice are important aspects in the nursing care of women with breast cancer. Patients with breast cancer consistently identify communication as an area of central importance. The nurse, specialist or otherwise, has an important role in addressing patients' needs following diagnosis and treatment for breast cancer.

Adaptation, Psychological↗
PubMed1998

Breast cancer. Part 2: Management.

Management of breast cancer will depend on its stage and degree of spread. Management may be by surgery, chemotherapy, endocrine therapy or radiotherapy, or a combination of some or all of these.

Antineoplastic Agents↗
PubMed1997

Fossils, genes and the evolution of animal limbs.

The morphological and functional evolution of appendages has played a crucial role in the adaptive radiation of tetrapods, arthropods and winged insects. The origin and diversification of fins, wings and other structures, long a focus of palaeontology, can now be approached through developmental genetics. Modifications of appendage number and architecture in each phylum are correlated with regulatory changes in specific patterning genes. Although their respective evolutionary histories are unique, vertebrate, insect and other animal appendages are organized by a similar genetic regulatory system that may have been established in a common ancestor.

Adaptation, Physiological↗
PubMed1997

Development of a sensitive method for quantitation of ABT-089 in plasma using fluorescence labeling with 7-fluoro-4-nitrobenzo-2-oxa-1,3-diazole.

A high-performance liquid chromatography method for the quantitation of ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine] (I), a new structural type of cholinergic channel modulators (ChCM), is described in this paper using 7-fluoro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-F) as a fluorescent-labeling reagent. The method combined an optimized liquid-liquid extraction from plasma followed by pre-column derivatization to yield a fluorescence product. The selectivity, sensitivity, and reproducibility of this method were found to be excellent. This method was applied to the determination of ng/ml plasma and tissue levels of ABT-089 and similar compounds in biological samples.

4-Chloro-7-nitrobenzofurazan↗
PubMed1997

Evolution of the entire arthropod Hox gene set predated the origin and radiation of the onychophoran/arthropod clade.

BACKGROUND: Dramatic changes in body size and pattern occurred during the radiation of many taxa in the Cambrian, and these changes are best documented for the arthropods. The sudden appearance of such diverse body plans raises the fundamental question of when the genes and the developmental control systems that regulate these designs evolved. As Hox genes regulate arthropod body patterns, the evolution of these genes may have played a role in the origin and diversification of the arthropod body plan from a homonomous ancestor. To trace the origin of arthropod Hox genes, we examined their distribution in a myriapod and in the Onychophora, a sister group to the arthropods. RESULTS: Despite the limited segmental diversity within myriapods and Onychophora, all insect Hox genes are present in both taxa, including the trunk Hox genes Ultrabithorax and abdominal-A as well as an ortholog of the fushi tarazu gene. Comparative analysis of Hox gene deployment revealed that the anterior boundary of expression of trunk Hox genes has shifted dramatically along the anteroposterior axis between Onychophora and different arthropod classes. Furthermore, we found that repression of expression of the Hox target gene Distal-less is unique to the insect lineage. CONCLUSIONS: A complete arthropod Hox gene family existed in the ancestor of the onychophoran/arthropod clade. No new Hox genes were therefore required to catalyze the arthropod radiation; instead, arthropod body-plan diversity arose through changes in the regulation of Hox genes and their downstream targets.

Amino Acid Sequence↗
PubMed1997

Drosophila Mad binds to DNA and directly mediates activation of vestigial by Decapentaplegic.

The TGF-beta (transforming growth factor-beta)-related signalling proteins, including Decapentaplegic (Dpp) in Drosophila-and bone morphogenic proteins and activin in vertebrates, affect the growth and patterning of a great variety of structures. However, the mechanisms by which these ligands regulate gene expression are not understood. Activation of complexes of type I with type II receptors results in the phosphorylation and nuclear localization of members of the SMAD protein family, which are thought to act as co-activators of transcription, perhaps in conjunction with sequence-specific cofactors. Here we show that the amino-terminal domain of the Drosophila Mothers against dpp protein (Mad), a mediator of Dpp signalling, possesses a sequence-specific DNA-binding activity that becomes apparent when carboxy-terminal residues are removed. Mad binds to and is required for the activation of an enhancer within the vestigial wing-patterning gene in cells across the entire developing wing blade. Mad also binds to Dpp-response elements in other genes. These results suggest that Dpp signalling regulates gene expression by activating Mad binding to target gene enhancers.

Animals↗
PubMed1996

Challenges to clinical deployment of upper limb neuroprostheses.

The technology for functional neuromuscular stimulation (FNS) as a means of providing upper limb function to people with tetraplegia has been under development by three clinical research groups for almost two decades. This paper presents the current status of the clinical trials of three FNS systems: a noninvasive system built into a cosmetic forearm splint, a 30-channel percutaneous system, and an 8-channel implantable system. The complexity of FNS systems and the unique characteristics of the individuals to whom they are applied combine to create many clinical and technical challenges that must be addressed before the devices can be deployed. The emerging challenges to widespread clinical introduction of FNS systems for hand and arm function are identified and analyzed. In addition to the demands of designed and conducting the clinical trials to satisfy regulatory requirements, the lack of knowledge, skepticism, and the complacency on the part of potential FNS recipients, as well as of rehabilitation professionals, must be overcome through education and careful consideration of economic and societal factors in the design of clinical systems.

Arm↗
PubMed1996

Pre-term pre-labour amniorrhexis.

In pregnancies complicated by pre-term pre-labour aminorrhexis, there is a risk of intra-uterine infection, which is associated with maternal and perinatal mortality and morbidity. The causes of neonatal death in pregnancies with aminorrhexis are prematurity, pulmonary hypoplasia and sepsis. In the management of pregnancies with pre-term pre-labour amniorrhexis, it is essential to distinguish between those with and without intra-uterine infection. If there is no infection at presentation, it is unlikely that this will develop, and in such cases there is no benefit from hospitalization, bed rest, prophylactic tocolytics or antibiotics. The group with evidence of intra-uterine infection go into spontaneous labour within a few days of amniorrhexis; in this group, the main determinant for the appropriate management is the gestational age at amniorrhexis.

Anti-Inflammatory Agents↗
PubMed1995

The development of crustacean limbs and the evolution of arthropods.

Arthropods exhibit great diversity in the position, number, morphology, and function of their limbs. The evolutionary relations among limb types and among the arthropod groups that bear them (insects, crustaceans, myriapods, and chelicerates) are controversial. Here, the use of molecular probes, including an antibody to proteins encoded by arthropod and vertebrate Distal-less (Dll and Dlx) genes, provided evidence that common genetic mechanisms underlie the development of all arthropod limbs and their branches and that all arthropods derive from a common ancestor. However, differences between crustacean and insect body plans were found to correlate with differences in the deployment of particular homeotic genes and in the ways that these genes regulate limb development.

Amino Acid Sequence↗