<p><!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:HyphenationZone>21</w:HyphenationZone> <w:PunctuationKerning /> <w:ValidateAgainstSchemas /> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:Compatibility> <w:BreakWrappedTables /> <w:SnapToGridInCell /> <w:WrapTextWithPunct /> <w:UseAsianBreakRules /> <w:DontGrowAutofit /> </w:Compatibility> <w:BrowserLevel>MicrosoftInternetExplorer4</w:BrowserLevel> </w:WordDocument> </xml><![endif]--><!--[if gte mso 9]><xml> <w:LatentStyles DefLockedState="false" LatentStyleCount="156"> </w:LatentStyles> </xml><![endif]--> <!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; line-height:150%; mso-pagination:widow-orphan; font-size:12.0pt; mso-bidi-font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} p.Standardmedluft, li.Standardmedluft, div.Standardmedluft {mso-style-name:"Standard med luft"; margin-top:14.0pt; margin-right:0cm; margin-bottom:0cm; margin-left:0cm; margin-bottom:.0001pt; text-align:justify; line-height:150%; mso-pagination:widow-orphan; font-size:12.0pt; mso-bidi-font-size:10.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 70.85pt 2.0cm 70.85pt; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> <!--[if gte mso 10]><mce:style><! /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} --><!--[endif]--></p><p>Transvection is a widespread phenomenon affecting chromosomal and gene function. There are many examples of epigenetic machineries controlling gene regulation. Nuclear Lamin proteins could have this function. This project shows <em>zeste</em> dependent transvection<strong> </strong>in loss-of-function<strong> </strong><em>lamin</em> mutants in <em>Drosophila melanogaster</em>.<strong> </strong>The <em>zeste</em> locus<strong> </strong>encodes a regulatory gene product affecting the expression of other loci, e.g. <em>white</em>. No transvection effect in loss-of-function <em>lamin </em>mutants has so far been shown. The effect of homozygosity versus heterozygosity of <em>lamin</em> on <em>zeste</em>-dependent transvection at paired <em>white</em> loci was analysed by crossing fruit flies to get homozygous<em> </em><em>z¹</em>; <em>lam</em>^D395 individuals. Whether or not the <em>zeste (z¹</em>) transvection effect on <em>white</em> was affected by <em>lam</em> ^D395 loss-of-function mutation was determined by comparing the eye colour phenotypes of double mutant <em>z¹</em>; <em>lam</em>^D395 females to that of <em>z¹/Y</em>; <em>lam</em>^D395 males, which were used as an internal negative control since they are hemizygous for <em>zeste</em> that is located on the X chromosome. Females homozygous for <em>z¹</em> and <em>lam</em>^D395 displayed the <em>z¹</em>-characteristic yellow eye colour. The conclusion is that <em>zeste</em>-dependent transvection effect at <em>white</em> also occurs in <em>lamin</em> mutants. Future research on transvection is needed in order to understand the exact mechanisms of gene regulation. Even gene therapies for some human diseases can take advantage of <em>trans</em>-acting sequences to correct gene expression.</p><p> </p>

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Signal processing in the visual system is mediated by classic neurotransmission and neuropeptidergic modulatory pathways. In Dipteran insects, especially in the fruitfly Drosophila melanogaster, the morphology of the visual system is very well described. However neurotransmitter and neuropeptidergic circuits within the optic lobe neuropil are only partially known. Using several transgenic fly lines and antibodies we determined the localization of the classical neurotransmitters GABA, acetylcholine and glutamate in the visual system, and their putative targets via detecting several neurotransmitter receptors. We paid particular attention to the peripheral neuropil layer called the lamina, where the light signals are filtered, channeled and amplified (Paper I). We discovered four new types of efferent tangential neurons branching distally to the lamina. Among them was the first neuropeptidergic neuron (LMIo) in this region of Drosophila. The LMIo expresses myoinhibitory peptide (MIP) and has its cell body located close to the main lateral clock neurons that express the neuropeptide pigment-dispersing factor (PDF)(Paper II). Since in other Dipteran species PDF is expressed in processes distally to the lamina, we performed comparative anatomical studies of the MIP, PDF, Ion Transport Peptide (ITP) and serotonin (5-HT) distribution in the visual system of the flies Drosophila and Calliphora. Our data suggest that PDF signaling distal to the lamina of the blowfly might be replaced by MIP signaling in the fruitfly, while ITP and 5-HT expression is conserved in the two species (Paper III). Serotonin is crucial in light adaptation during the daily light-dark cycles. We analyzed putative serotonergic circuits in the lamina. We found that LMIo neurons express the inhibitory receptor 5-HT1A, while 5-HT1B and 5-HT2 are both expressed in the epithelial glia of the lamina. Another novel wide-field neuron with lamina branches expresses the excitatory serotonin receptor 5-HT7. Our studies have identified a fairly complex neuronal circuitry in the tangential plexus above the lamina. (Paper IV). Finally we tested circadian locomotor activity rhythms in flies with the GABAB receptor knocked down on the lateral PDF-expressing clock neurons. We observed significant changes in the activity periods and diminished strength of rhythmicity during DD suggesting a modulatory role of GABA in clock function (Paper V). / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript. Paper 5: Manuscript.

The nuclear lamina is a filamentous network that underlies the nuclear envelope. Lamina components include the family of LEM domain (LEM-D) proteins, named for LAP2, emerin and MAN1. Mutations in genes encoding LEM-D proteins cause tissue-restricted human disease, even though these genes are globally expressed. To understand the contributions of the LEM-D proteins to nuclear lamina function, investigations of the Drosophila LEM-D proteins was undertaken. The Drosophila genome encodes four LEM-D proteins and this thesis describes work done on the Drosophila homologues of MAN1 and emerin, Drosophila MAN1 (dMAN1) and Otefin (Ote). Chapter 2 describes the generation and phenotypic analyses of dMAN1 mutants. These mutants display a range of tissue-specific defects associated with an increase in BMP/Dpp signaling. This suggests that dMAN1 downregulates BMP/Dpp signaling at the nuclear periphery. Chapter 3 describes the identification and phenotypic analyses of ote mutants. Loss of Ote is associated with a tissue-specific defect of the female germline where ote mutant females display defects in germline stem cell (GSC) maintenance. Loss of Ote causes defects in the germline cells, the cap cells of GSC niche and an increased sensitivity to Dpp signaling in both germline and somatic cells. These findings support models suggesting that laminopathies arise from dysfunction of the homeostasis in stem cell populations. Taken together, these studies suggest that the nuclear lamina may play tissue-specific roles through regulation of signal transduction pathways. Our data also support the use of Drosophila as a system to elucidate the mechanistic basis of diseases associated with defects in the nuclear lamina.

No description available.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18546号 / 医博第3939号 / 新制||医||1006(附属図書館) / 31446 / 京都大学大学院医学研究科医学専攻 / (主査)教授 武田 俊一, 教授 松田 文彦, 教授 小松 賢志 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

Lamina emergent mechanisms (LEMs) are a subset of compliant mechanisms which are fabricated from planar materials; use compliance, or flexibility of the material, to transfer energy; and have motion that emerges out of the fabrication plane. LEMs provide potential design advantages by reducing the number of parts, reducing cost, reducing weight, improving recyclability, increasing precision, and eliminating assembly, to name a few. However, there are inherent design and modeling challenges including complexities in large, non-linear deflections, singularities that exist when leaving the planar state, and the coupling of material properties and geometry in predicting mechanism behavior. This thesis examines the planar and spherical LEMs and their relation to origami. Origami, the art of paper folding, is used to better understand spherical LEMs and flat-folding mechanisms in general. All single-layer planar four-bar LEMs are given with their respective layouts. These are all change-point pinned mechanisms (i.e. no slider cranks). Graph representations are used to show the similarities between action origami and mechanisms. Origami principles of flat-folding are shown to be analogous to principles of mechanisms including rules for assembly and motion.

There is an increasing need for compact mechanical systems that can accomplish sophisticated tasks. Technologies like ortho-planar and lamina emergent mechanisms (LEMs) have been developed to satisfy needs like these by stowing in planar sheets from which they emerge to perform their function. They can be compact, lightweight, monolithic, scalable, and can withstand harsh environments. They are limited, however, by their base element---planar surfaces. Applications requiring these advantages often include curved surfaces, like aircraft wings, needles, and automotive bodies. In this research, developable mechanisms are presented as a solution to satisfy the need for mechanisms that can conform to or emerge from curved surfaces. Foundational principles which enable designers to leverage the advantages of developable mechanisms are described herein.Developable mechanisms result from the union of mechanisms and developable surfaces. Developable (flattenable) surfaces act as a fitting medium because of their particular advantages in manufacturability and how well they accompany four-link, revolute joint (4R) mechanisms. The definition, including specific qualifying criteria, for developable mechanisms is given. Certain types of mechanisms and classes of developable surfaces can be combined to satisy that criteria. Developable mechanism sub-classes are defined as planar, cylindrical, conical and tangent developable mechanisms. It is shown that planar and spherical mechanisms can be used to create cylindrical and conical developable mechanisms, respectively. The Bennett and other 7R mechanisms can be used for tangent developable mechanisms. Steps for developable mechanism creation are presented, and several physical prototypes are provided to demonstrate feasibility.The cylindrically curved Lamina Emergent Torsional (LET) joint is offered as an enabling technology for producing compliant developable mechanisms. A mathematical model predicting force-deflection and stress behavior is provided and verified. The relationship between stiffness and strain energy storage for curved sheet materials with incorporated LET joints is explored. Material shape factors are used to derive an effective modulus of elasticity and an effective modulus of resilience, which are compared with original values on an Ashby plot. While there is a decrease in the modulus of resilience, there is a much more significant decrease in the modulus of elasticity. A material performance index is provided as an example for determining suitable materials for a given stiffness-reduction application. It is shown that the cylindrically curved LET joint makes it possible to create highly flexible joints that maintain much of their energy storage capability in curved sheet materials.

No description available.

No description available.