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R Kraut

Publications and source records attributed to R Kraut.

18 recordsLinked to original sources

A gain-of-function screen for genes controlling motor axon guidance and synaptogenesis in Drosophila.

BACKGROUND: The neuromuscular system of the Drosophila larva contains a small number of identified motor neurons that make genetically defined synaptic connections with muscle fibers. We drove high-level expression of genes in these motor neurons by crossing 2293 GAL4-driven EP element lines with known insertion site sequences to lines containing a pan-neuronal GAL4 source and UAS-green fluorescent protein elements. This allowed visualization of every synapse in the neuromuscular system in live larvae. RESULTS: We identified 114 EPs that generate axon guidance and/or synaptogenesis phenotypes in F1 EP x driver larvae. Analysis of genomic regions adjacent to these EPs defined 76 genes that exhibit neuromuscular gain-of-function phenotypes. Forty-one of these (known genes) have published mutant alleles; the other 35 (new genes) have not yet been characterized genetically. To assess the roles of the known genes, we surveyed published data on their phenotypes and expression patterns. We also examined loss-of-function mutants ourselves, identifying new guidance and synaptogenesis phenotypes for eight genes. At least three quarters of the known genes are important for nervous system development and/or function in wild-type flies. CONCLUSIONS: Known genes, new genes, and a set of previously analyzed genes with phenotypes in the Adh region display similar patterns of homology to sequences in other species and have equivalent EST representations. We infer from these results that most new genes will also have nervous system loss-of-function phenotypes. The proteins encoded by the 76 identified genes include GTPase regulators, vesicle trafficking proteins, kinases, and RNA binding proteins.

Animals↗

Endoresection of the iris and ciliary body in epithelial downgrowth.

We present a case of epithelial downgrowth with intractable glaucoma after multiple intraocular surgeries. The eye was successfully managed with a pars plana approach. The iris and epithelial tissue over the ciliary body were removed with intraocular scissors and a vitrector combined with unipolar diathermy and endophotocoagulation. The use of moderate hypotensive anesthesia may have helped prevent intraoperative hemorrhage. During more than 3 years of follow-up, intraocular pressure ranged from 13 to 19 mm Hg, visual acuity was 20/80 with aphakic correction with a rigid gas-permeable lens, and there was no recurrence of epithelial downgrowth.

Adolescent↗

Internet paradox. A social technology that reduces social involvement and psychological well-being?

The Internet could change the lives of average citizens as much as did the telephone in the early part of the 20th century and television in the 1950s and 1960s. Researchers and social critics are debating whether the Internet is improving or harming participation in community life and social relationships. This research examined the social and psychological impact of the Internet on 169 people in 73 households during their first 1 to 2 years on-line. We used longitudinal data to examine the effects of the Internet on social involvement and psychological well-being. In this sample, the Internet was used extensively for communication. Nonetheless, greater use of the Internet was associated with declines in participants' communication with family members in the household, declines in the size of their social circle, and increases in their depression and loneliness. These findings have implications for research, for public policy and for the design of technology.

Adolescent↗

On the roles of inscuteable in asymmetric cell divisions in Drosophila.

Three processes requiring insc, protein localization, RNA localization, and mitotic spindle orientation, appear to be tightly correlated but nevertheless independent. The apical cortical localization of Insc protein occurs prior to mitosis and precedes the basal localization of Pros, Numb, and pros RNA. In insc null mutants, neuroblasts divide in more random orientations and fail to correctly localize Pros, Numb, and pros RNA to their correct position during mitosis. Our results suggest that asymmetric localization of Insc during interphase functions to establish positional information for spindle orientation and the basal localization of Numb, Pros, and pros RNA during mitosis. Insc probably interacts with a number of interacting partners in order to effect its various functions. One of its partners, Stau, is involved exclusively in the process of RNA localization.

Amino Acid Sequence↗

Role of inscuteable in orienting asymmetric cell divisions in Drosophila.

Drosophila neuroblasts and epithelial cells in the procephalic neurogenic region divide perpendicular to the surface, and segregate the proteins Numb and Prospero into the basal daughter cell. We demonstrate here that orientation of the mitotic spindle and correct localization of Numb and Prospero in these cells require the inscuteable gene. Moreover, ectopic expression of inscuteable in other epithelial cells leads to spindle reorientation. The Inscuteable protein localizes to the apical cell cortex before mitosis, suggesting that Inscuteable functions in establishing polarity for asymmetric cell division.

Actins↗

Zygotic Drosophila E-cadherin expression is required for processes of dynamic epithelial cell rearrangement in the Drosophila embryo.

Dynamic epithelial reorganization is essential for morphogenesis of various organs. In Drosophila embryos, for example the Malpighian tubule is generated by cellular rearrangement of a preexisting epithelium and the tracheal network is formed by outgrowth, branching, and fusion of epithelial vesicles. Here we report that the previously identified locus shotgun (shg) encodes DE-cadherin, an epithelial cell-cell adhesion molecule of the classic cadherin type and that zygotic shg mutations rather specifically impair processes of the dynamic epithelial morphogenesis. In the mutants, the Malpighian tubule disintegrated into small spherical structures, and the tracheal network formation was blocked in selected steps. The malformation of these organs could be rescued by overexpression of DE-cadherin cDNA under a heat shock promoter. Unexpectedly, the zygotic null condition did not severely affect general epithelial organization; most epithelial tissues maintained not only their cell-cell associations but also their apicobasal polarity in the mutants. The zygotic null mutant retained a certain level of maternally derived DE-cadherin molecules until the end of embryogenesis. These results suggest that zygotic DE-cadherin expression is critical for the rearrangement processes of epithelial cells, whereas the maternally derived DE-cadherin may serve only for the maintenance of the static architecture of the epithelia.

Animals↗

inscuteable, a neural precursor gene of Drosophila, encodes a candidate for a cytoskeleton adaptor protein.

In Drosophila, neural precursor genes are expressed in neural progenitor cells as the neuroblasts and sense organ mother cells. These genes are thought to control the fate and/or behavior of neural progenitor cells once their fate decision has been made. We have isolated and characterized a novel neural precursor gene, inscuteable, whose expression is coincident with sites of cell shape changes or cell and tissue movement in the embryo, e.g., neuroblasts, trachea, Malphigian tubules, and in pupal wing epithelia. The Inscuteable protein is localized to the apical submembranous surface of neuroblasts and other cell types and shows certain features common to a family of putative cytoskeletal associated proteins. The inscuteable mutant phenotype, together with these other observations, suggests a possible role for the protein in cytoskeleton organization.

Amino Acid Sequence↗

Use of Vicryl (polyglactin-910) mesh implant for repair of orbital floor fracture causing diplopia: a study of 28 patients over 5 years.

Over the past 5 years, Vicryl mesh (polyglactin-910) implants were used successfully to reconstruct the orbital floor in 28 patients with significant preoperative diplopia due to orbital floor fractures. The layered mesh is available in 26.5 x 24 cm sheets, each of which is folded onto itself into 24 layers and packaged; 24 layers are approximately 4 mm thick. Appropriately sized implants varying in thickness from 6 to 56 layers were used to cover and fill the orbital floor defect. Absorbable Vicryl mesh is well-tolerated by orbital tissues; since it is soft and pliable, it is unlikely to compress orbital structures such as the optic nerve, lacrimal sac, or extraocular muscles. A second surgical site necessary for autogenous implants is avoided. The Vicryl mesh implant is technically easy to insert and does not require fixation in the orbit. Because Vicryl mesh is absorbable, the risks associated with permanent alloplastic implants are reduced. Similarly, there is no potential spread of communicable disease with homologous tissue implants. Follow-up ranged from 1 month to 2 years (median, 13 months). None of the patients had late complications. The only complication was transient, low-grade eyelid inflammation in four patients.

Adolescent↗

The dorsal morphogen is a sequence-specific DNA-binding protein that interacts with a long-range repression element in Drosophila.

A gradient of the maternal morphogen dorsal (dl) establishes dorsal-ventral (D-V) polarity in the early Drosophila embryo. The dl concentration gradient is initiated by regulated nuclear transport, and only protein that enters nuclei is active in the D-V patterning process. Here we show that dl is a DNA-binding protein that specifically interacts with distal sequences of the zerknüllt (zen) promoter, one of the genetic targets of the morphogen. These zen sequences have the properties of a silencer element and can act over long distances to repress the expression of a heterologous promoter. The dl protein recognizes a sequence motif similar to that of the mammalian transcriptional activator NF-kappa B, which was shown to contain extensive homology with dl and the oncoprotein rel. We present evidence that the DNA-binding activity of the dl protein is mediated by the region of homology (the rel domain) conserved in the rel and NF-kappa B proteins.

Animals↗

Transcriptional regulation of a pair-rule stripe in Drosophila.

The periodic, seven-stripe pattern of the primary pair-rule gene even-skipped (eve) is initiated by crude, overlapping gradients of maternal and gap gene proteins in the early Drosophila embryo. Previous genetic studies suggest that one of the stripes, stripe 2, is initiated by the maternal morphogen bicoid (bcd) and the gap protein hunchback (hb), while the borders of the stripe are formed by selective repression, involving the gap protein giant (gt) in anterior regions and the Krüppel (Kr) protein in posterior regions. Here, we present several lines of evidence that are consistent with this model for stripe 2 expression, including in vitro DNA-binding experiments and transient cotransfection assays in cultured cells. These experiments suggest that repression involves a competition or short-range quenching mechanism, whereby the binding of gt and Kr interferes with the binding or activity of bcd and hb activators at overlapping or neighboring sites within the eve stripe 2 promoter element. Such short-range repression could reflect a general property of promoters composed of multiple, but autonomous regulatory elements.

Amino Acid Sequence↗

Spatial regulation of the gap gene giant during Drosophila development.

We describe the regulated expression of the segmentation gene giant (gt) during early embryogenesis. The gt protein is expressed in two broad gradients in precellular embryos, one in anterior regions and the other in posterior regions. Double immunolocalization studies show that the gt patterns overlap with protein gradients specified by the gap genes hunchback (hb) and knirps (kni). Analysis of all known gap mutants, as well as mutations that disrupt each of the maternal organizing centers, indicate that maternal factors are responsible for initiating gt expression, while gap genes participate in the subsequent refinement of the pattern. The maternal morphogen bicoid (bcd) initiates the anterior gt pattern, while nanos (nos) plays a role in the posterior pattern. Gene dosage studies indicate that different thresholds of the bcd gradient might trigger hb and gt expression, resulting in overlapping but noncoincident patterns of expression. We also present evidence that different concentrations of hb protein are instructive in defining the limits of kni and gt expression within the presumptive abdomen. These results suggest that gt is a bona fide gap gene, which acts with hb, Krüppel and kni to initiate striped patterns of gene expression in the early embryo.

Animals↗

Mutually repressive interactions between the gap genes giant and Krüppel define middle body regions of the Drosophila embryo.

The gap genes play a key role in establishing pair-rule and homeotic stripes of gene expression in the Drosophila embryo. There is mounting evidence that overlapping gradients of gap gene expression are crucial for this process. Here we present evidence that the segmentation gene giant is a bona fide gap gene that is likely to act in concert with hunchback, Krüppel and knirps to initiate stripes of gene expression. We show that Krüppel and giant are expressed in complementary, non-overlapping sets of cells in the early embryo. These complementary patterns depend on mutually repressive interactions between the two genes. Ectopic expression of giant in early embryos results in the selective repression of Krüppel, and advanced-stage embryos show cuticular defects similar to those observed in Krüppel- mutants. This result and others suggest that the strongest regulatory interactions occur among those gap genes expressed in nonadjacent domains. We propose that the precisely balanced overlapping gradients of gap gene expression depend on these strong regulatory interactions, coupled with weak interactions between neighboring genes.

Animals↗

Spatial regulation of zerknüllt: a dorsal-ventral patterning gene in Drosophila.

zerknüllt (zen) is one of approximately 10 zygotically active genes that control the differentiation of the dorsal-ventral (D/V) pattern during early embryogenesis in Drosophila. Past genetic analyses suggest that maternal factors repress the expression of zen in ventral regions, thereby restricting zen products to dorsal and dorsal-lateral regions of precellular embryos. Subsequent interactions with other zygotic D/V regulatory genes refine the zen pattern, restricting expression to the dorsal-most ectoderm. Here we describe the use of zen promoter fusions and P-element transformation to identify cis elements that are responsible for the complex spatial pattern of zen expression. The zen promoter shows a two-tier organization: Distal sequences mediate its initial response to maternal factors, whereas proximal sequences are responsible for the refinement of the pattern in older embryos. The distal regulatory element has the property of a silencer (or anti-enhancer) element and can act over a distance to repress ventral expression of a heterologous promoter. Also, we discuss evidence that proximal promoter sequences interact with factors that may be modulated by a cell-cell communication pathway.

Animals↗

Restoration of a total maxillectomy patient using endosseous implants.

A vehicular accident resulted in a total maxillectomy for the patient compromising deglutition, mastication, speech, and appearance. Bone grafting provided a site for the placement of endosseous implants. The implants were used as stabilization for a prosthesis that resolved these problems. The prosthesis consisted of a multipart substructure attached to the implants. The superstructure was in intimate contact with the substructure, obturated the defect, and provided occlusal contacts, palatal form, and lip support.

Adult↗