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Biomedical subjects

D L Brower

Publications and source records attributed to D L Brower.

At least 19 recordsLinked to original sources
PubMed2004

Measurement of the Hall dynamo effect during magnetic reconnection in a high-temperature plasma.

The fluctuation-induced Hall electromotive force, [deltaJ x deltaB]/nee, is experimentally measured in the high-temperature interior of a reversed-field pinch plasma by a fast Faraday rotation diagnostic. It is found that the Hall dynamo effect is significant, redistributing (flattening) the equilibrium core current near the resonant surface during a reconnection event. These results imply that effects beyond single-fluid MHD are important for the dynamo and magnetic reconnection.

Journal Article↗
PubMed2003

Electron heat transport measured in a stochastic magnetic field.

New profile measurements have allowed the electron thermal diffusivity profile to be estimated from power balance in the Madison Symmetric Torus where magnetic islands overlap and field lines are stochastic. The measurements show that (1) the electron energy transport is conductive not convective, (2) the measured thermal diffusivities are in good agreement with numerical simulations of stochastic transport, and (3) transport is greatly reduced near the reversal surface where magnetic diffusion is small.

Journal Article↗
PubMed2003

Measurement of internal magnetic field fluctuations in a reversed-field pinch by Faraday rotation.

Magnetic field fluctuations (and the associated current perturbation) have been measured in the core of a high-temperature reversed-field pinch using a newly developed fast-polarimetry system. Radial magnetic field fluctuation levels of approximately 1% are measured in standard-reversed-field pinch discharges which increase to approximately 4% during the sawtooth crash (enhanced dynamo). The fluctuation level is reduced fourfold for high-confinement plasmas where the core-resonant tearing modes are suppressed.

Journal Article↗
PubMed2002

Measurement of the current-density profile and plasma dynamics in the reversed-field pinch.

First measurements of the current-density profile in the core of a high-temperature reversed-field pinch are presented. The current-density profile is observed to peak during the sawtooth cycle and broaden promptly at the crash. This change in profile can be linked to magnetic relaxation and the dynamo which is predicted to drive antiparallel current in the plasma core. For high-confinement discharges, the dynamo is suppressed and the current-density profile is observed to strongly peak.

Journal Article↗
PubMed2001

Reduced edge instability and improved confinement in the MST reversed-field pinch.

Improved confinement has been achieved in the MST through control of the poloidal electric field, but it is now known that the improvement has been limited by bursts of an edge-resonant instability. Through refined poloidal electric field control, plus control of the toroidal electric field, we have suppressed these bursts. This has led to a total beta of 15% and a reversed-field-pinch-record estimated energy confinement time of 10 ms, a tenfold increase over the standard value which for the first time substantially exceeds the confinement scaling that has characterized most reversed-field-pinch plasmas.

Journal Article↗
PubMed2001

Intron dynamics and the evolution of integrin beta-subunit genes: maintenance of an ancestral gene structure in the coral, Acropora millepora.

We have determined the genomic structure of an integrin beta-subunit gene from the coral, Acropora millepora. The coding region of the gene contains 26 introns, spaced relatively uniformly, and this is significantly more than have been found in any integrin beta-subunit genes from higher animals. Twenty-five of the 26 coral introns are also found in a beta-subunit gene from at least one other phylum, indicating that the coral introns are ancestral. While there are some suggestions of intron gain or sliding, the predominant theme seen in the homologues from higher animals is extensive intron loss. The coral baseline allows one to infer that a number of introns found in only one phylum of higher animals result from frequent intron loss, as opposed to the seemingly more parsimonious alternative of isolated intron gain. The patterns of intron loss confirm results from protein sequences that most of the vertebrate genes, with the exception of beta4, belong to one of two beta subunit families. The similarity of the patterns within each of the beta1,2,7 and beta3,5,6,8 groups indicates that these gene structures have been very stable since early vertebrate evolution. Intron loss has been more extensive in the invertebrate genes, and obvious patterns have yet to emerge in this more limited data set.

Amino Acid Sequence↗
PubMed2001

Nuclear import of activated D-ERK by DIM-7, an importin family member encoded by the gene moleskin.

The initiation of gene expression in response to Drosophila receptor tyrosine kinase signaling requires the nuclear import of the MAP kinase, D-ERK. However, the molecular details of D-ERK translocation are largely unknown. In this regard, we have identified D-Importin-7 (DIM-7), the Drosophila homolog of vertebrate importin 7, and its gene moleskin. DIM-7 exhibits a dynamic nuclear localization pattern that overlaps the spatial and temporal profile of nuclear, activated D-ERK. Co-immunoprecipitation experiments show that DIM-7 associates with phosphorylated D-ERK in Drosophila S2 cells. Furthermore, moleskin mutations enhance hypomorphic and suppress hypermorphic D-ERK mutant phenotypes. Deletion or mutation of moleskin dramatically reduces the nuclear localization of activated D-ERK. Directly linking DIM-7 to its nuclear import, this defect can be rescued by the expression of wild-type DIM-7. Mutations in the Drosophila Importin beta homolog Ketel, also reduce the nuclear localization of activated D-ERK. Together, these data indicate that DIM-7 and Ketel are components of the nuclear import machinery for activated D-ERK.

Active Transport, Cell Nucleus↗
PubMed1998

The PS integrins are required for a regulatory event during Drosophila wing morphogenesis.

The PS1 and PS2 integrins are required for morphogenesis of the adult Drosophila wing. Clonal analysis experiments have shown that both integrins are necessary to maintain adhesion between the dorsal and ventral wing epithelia. We have found that early in wing morphogenesis, the integrins are also required for a regulatory event, and this may explain why PS1 and PS2 must be expressed on opposite surfaces of the wing at the onset of pupariation. Overexpression of integrin subunits during this early phase can lead to separation of dorsal and ventral surfaces, and we present evidence here that this dominant phenotype (the Blistermaker phenotype) results from a gain of integrin function, as opposed to negative interference from free integrin subunits. A possible model for an integrin signaling requirement in the wing is discussed.

Animals↗
PubMed1998

Splice variants of the Drosophila PS2 integrins differentially interact with RGD-containing fragments of the extracellular proteins tiggrin, ten-m, and D-laminin 2.

Two new potential ligands of the Drosophila PS2 integrins have been characterized by functional interaction in cell culture. These potential ligands are a new Drosophila laminin alpha2 chain encoded by the wing blister locus and Ten-m, an extracellular protein known to be involved in embryonic pattern formation. As with previously identified PS2 ligands, both contain RGD sequences, and RGD-containing fragments of these two proteins (DLAM-RGD and TENM-RGD) can support PS2 integrin-mediated cell spreading. In all cases, this spreading is inhibited specifically by short RGD-containing peptides. As previously found for the PS2 ligand tiggrin (and the tiggrin fragment TIG-RGD), TENM-RGD induces maximal spreading of cells expressing integrin containing the alphaPS2C splice variant. This is in contrast to DLAM-RGD, which is the first Drosophila polypeptide shown to interact preferentially with cells expressing the alphaPS2 m8 splice variant. The betaPS integrin subunit also varies in the presumed ligand binding region as a result of alternative splicing. For TIG-RGD and TENM-RGD, the beta splice variant has little effect, but for DLAM-RGD, maximal cell spreading is supported only by the betaPS4A form of the protein. Thus, the diversity in PS2 integrins due to splicing variations, in combination with diversity of matrix ligands, can greatly enhance the functional complexity of PS2-ligand interactions in the developing animal. The data also suggest that the splice variants may alter regions of the subunits that are directly involved in ligand interactions, and this is discussed with respect to models of integrin structure.

Alternative Splicing↗
PubMed1998

The PS2 integrin ligand tiggrin is required for proper muscle function in Drosophila.

Tiggrin is a novel extracellular matrix ligand for the Drosophila PS2 integrins. We have used flanking P elements to generate a precise deletion of tiggrin. Most flies lacking tiggrin die as larvae or pupae. A few adults do emerge and these appear to be relatively normal, displaying only misshapen abdomens and a low frequency of wing defects. Examination of larvae shows that muscle connections, function and morphology are defective in tiggrin mutants. Muscle contraction waves that extend the length of the larvae are much slower in tiggrin mutants. Direct examination of bodywall muscles shows defects in muscle attachment sites, where tiggrin is specifically localized, and muscles appear thinner. Transgenes expressing tiggrin are capable of rescuing tiggrin mutant phenotypes. Transgenes expressing a mutant tiggrin, whose Arg-Gly-Asp (RGD) integrin recognition sequence has been mutated to Leu-Gly-Ala (LGA) show much reduced, but significant, rescuing ability. Cell spreading assays detect no interactions of this mutant tiggrin with PS2 integrins. Therefore, while the RGD sequence is critical for PS2 interactions and full activity in the whole fly, the mutant tiggrin retains some function(s) that are probably mediated by interactions with other ECM molecules or cell surface receptors

Abdomen↗
PubMed1997

Molecular evolution of integrins: genes encoding integrin beta subunits from a coral and a sponge.

The integrin family of cell surface receptors is strongly conserved in higher animals, but the evolutionary history of integrins is obscure. We have identified and sequenced cDNAs encoding integrin beta subunits from a coral (phylum Cnidaria) and a sponge (Porifera), indicating that these proteins existed in the earliest stages of metazoan evolution. The coral betaCn1 and, especially, the sponge betaPo1 sequences are the most divergent of the "beta1-class" integrins and share a number of features not found in any other vertebrate or invertebrate integrins. Perhaps the greatest difference from other beta subunits is found in the third and fourth repeats of the cysteine-rich stalk, where the generally conserved spacings between cysteines are highly variable, but not similar, in betaCn1 and betaPo1. Alternatively spliced cDNAs, containing a stop codon about midway through the full-length translated sequence, were isolated from the sponge library. These cDNAs appear to define a boundary between functional domains, as they would encode a protein that includes the globular ligand-binding head but would be missing the stalk, transmembrane, and cytoplasmic domains. These and other sequence comparisons with vertebrate integrins are discussed with respect to models of integrin structure and function.

Amino Acid Sequence↗
PubMed1996

Distinct spatial and temporal functions for PS integrins during Drosophila wing morphogenesis.

At the onset of pupariation in the Drosophila wing, the PS1 and PS2 integrins are expressed preferentially on the dorsal and ventral wing epithelia, respectively. Clonal analysis experiments have indicated that integrins are required to maintain the tight association of the wing surfaces. Surprisingly, we find that even in clones of cells lacking integrins the wing layers become apposed early in metamorphosis. However, following the normal period of wing separation, large integrin mutant clones do not become re-apposed in the pupa, and integrins are not organized in basal plaques in cells opposite a mutant clone. Paradoxically, our experiments indicate that at least one integrin function requires different integrins on the dorsal and ventral wing surfaces, however in some cases both alphaPS subunits can function to some degree on each wing surface. Finally, overexpression of an alphaPS subunit throughout the wing leads to a dominant wing blister phenotype, and the critical period for this phenotype is the beginning of pupariation. These data indicate that integrin requirements in wing morphogenesis can be separated into early (prepupal) and late (pupal) functions. The late function seems to reflect the traditional view of integrins as cell-matrix adhesion proteins. The early requirement, which probably requires dorsoventral segregation of PS1 and PS2, suggests functions for PS1 and PS2 in signaling events that regulate morphogenesis.

Animals↗
PubMed1995

Role of the PS integrins in Drosophila development.

The PS1 and PS2 integrins of Drosophila are heterodimers of alphaPS1betaPS and alphaPS2betaPS subunits, respectively, with very strong structural similarity to vertebrate integrins. Cell transfection experiments indicate that the PS integrins are receptors for extracellular matrix components and are functionally analogous to vertebrate integrins. Matrix ligands from Drosophila tissues have been identified for PS1 and PS2 integrins, using transformed cells and a cell-spreading assay. Mutations in all three subunit genes have been identified, and the phenotypes of mutants indicate that PS integrins are required for the proper morphogenesis of a number of embryonic tissues. Using methods to produce genetic mosaics and transformation of integrin transgenes into whole animals, integrin functions in adult morphogenesis also have been examined. In the pupal wing, integrins are critically required to maintain the connection between dorsal and ventral epithelia, and recent results suggest that in early pupal development, the integrins are acting as specific receptors, as opposed to a non-specific cell-matrix glue.

Animals↗
PubMed1995

Nonequivalent requirements for PS1 and PS2 integrin at cell attachments in Drosophila: genetic analysis of the alpha PS1 integrin subunit.

We report on the generation and phenotype of mutant alleles of multiple edematous wings (mew), the gene encoding the alpha PS1 subunit of the PS1 integrin of Drosophila. None of the six alleles examined makes detectable protein, and one allele results from a chromosome break near the middle of the translated sequence, so we are confident that we have described the null phenotype. In contrast to if (alpha PS2) and mys (beta PS) mutants, most mutant mew embryos hatch, to die as larvae. Mutant mew embryos display abnormal gut morphogenesis but, unlike mys or if embryos, there is no evidence of defects in the somatic muscles. Thus, the complementary distributions of PS1 (alpha PS1 beta PS) and PS2 (alpha PS2 beta PS) integrin on tendon cells and muscle, respectively, do not reflect equivalent requirements at the myotendinous junction. Dorsal herniation, characteristic of the mys lethal phenotype, is not observed in mew or in mew if embryos. Clonal analysis experiments indicate that eye morphogenesis is disrupted in mew clones, but if clones in the eye are relatively normal in morphology. Adult wings display blisters around large dorsal but not ventral mew clones. In contrast to dorsal mys clones, small mew patches do not necessarily display morphogenetic abnormalities. Thus, another integrin in addition to PS1 appears to function on the dorsal wing surface.

Alleles↗
PubMed1994

Tiggrin, a novel Drosophila extracellular matrix protein that functions as a ligand for Drosophila alpha PS2 beta PS integrins.

Genetic and other studies of Drosophila integrins have implicated these extracellular matrix receptors in various morphogenetic events, but identification of their endogenous ligands has been elusive. We report the biochemical purification and cloning of tiggrin, a novel extracellular matrix protein from Drosophila. This 255 x 10(3) M(r) polypeptide contains the potential integrin recognition sequence Arg-Gly-Asp (RGD) and 16 repeats of a novel 73-77 amino acid motif. The tiggrin gene is at chromosome locus 26D1-2 and is expressed by embryonic hemocytes and fat body cells. Tiggrin protein is detected in matrices, especially at muscle attachment sites that also strongly express integrins. Tiggrin-coated surfaces support primary embryo cell culture and provide excellent substrates for alpha PS2 beta PS integrin-mediated cell spreading. Soluble RGD-peptides inhibit this cell spreading.

Amino Acid Sequence↗
PubMed1994

The role of apterous in the control of dorsoventral compartmentalization and PS integrin gene expression in the developing wing of Drosophila.

During the development of Drosophila appendages from imaginal discs lineage restrictions appear that prevent dividing cells from crossing between regionally distinct compartments. These compartments correspond not only to regions of cell lineage restrictions but also to regions of specific gene expression. When compartments were first discovered, it was proposed that their formation relied on compartment-specific 'selector' gene activity; engrailed is thought to play such a role for the early-arising anterior-posterior restriction. Recent results suggest that the dorsally expressed transcription factor encoded by apterous may control dorsoventral identity in the wing. In this study we use mosaic analysis to show that apterous maintains the late-arising dorsoventral lineage restriction in a manner that strongly supports the selector gene hypothesis: loss of apterous function from dorsal cells after the formation of the boundary causes them to cross into the ventral compartment. Moreover, we show that apterous plays a role controlling patterns of gene expression in the developing wing disc. The PS1 and PS2 integrins are normally expressed in primarily dorsal-specific and ventral-specific patterns, respectively. We show that ectopic expression of apterous induces ectopic ventral expression of PS1 integrin and alpha PS1 mRNA, while loss of apterous can induce the ectopic dorsal expression of PS2 integrin. Thus, apterous plays a selector-like role both in terms of the control of lineage restrictions and the regulation of downstream gene expression.

Animals↗
PubMed1993

PS2 integrin requirements in Drosophila embryo and wing morphogenesis.

The Drosophila inflated (if) gene encodes the alpha PS2 subunit of the PS integrins. We describe the generation of new if mutations, their lethal embryonic phenotype, and experiments that examine the spatial and temporal requirements for integrins in adult wing morphogenesis. Embryos hemizygous for either new allele, ifA7 or ifB2, make reduced amounts of alpha PS2. In a variety of genetic tests, these alleles behave similarly to ifk27e, which makes no detectable alpha PS2, and all three alleles display the same embryonic phenotype. We therefore conclude that all of the lethal alleles retain little or no wild-type alpha PS2 function. As seen for strong mutations at the myospheroid (mys) locus, which encodes the beta PS integrin subunit, if mutants show extreme defects in somatic muscle attachments and in midgut morphogenesis. Unlike mys, however, there is no dorsal herniation of the if mutant embryos. With respect to wing morphogenesis, clonal analysis experiments demonstrate that if+ function is required only in cells of the ventral wing surface. We have rescued the wing blister phenotype of double mutants for the hypomorphic mysnj42 and if3 alleles using a heat shock-inducible mys+ transgene. By varying times of transgene induction, we find that integrin function is required from very early in metamorphosis until at least the last 24-48 hr of wing development.

Alleles↗