The Role of Vimentin in Tissue Repair and Cell Growth

Microfilaments, microtubules, and intermediate filaments serve as the cytoskeleton of the cell and form a complex network by interacting with cytoskeleton-associated proteins. The cytoskeleton provides a framework for the cell and regulates different cellular functions. Intermediate filaments form a large family of proteins, which are classified into different groups based on their structure and tissue expression pattern. Epithelial cells undergo epithelial mesenchymal transitions (EMT) during embryonic development, wound healing, cancer, and fibrosis, to become proliferative, and migratory in nature. Vimentin is a well-known EMT marker, but its role in EMT is not well characterized. This thesis work investigated the role of vimentin in EMT during the wound healing process, cell growth, and autoimmunity. In Vim-/- mice, delayed wound healing due to defects in EMT signaling, keratinocyte cell migration, fibroblast cell proliferation, and collagen deposition. Fibroblasts play an essential role in normal development and wound healing. We observed that a lack of vimentin resulted in reduced fibroblast cell size and due to deficient mTOR signaling. Vimentin affected mTOR signaling by modulating Rag GTPase activity, consequently regulating cell size and autophagy. We also found that vimentin expression was increased in regulatory Treg cells, which control autoimmune response, and this increase in expression was mediated through TGF-β1. This thesis work provides evidence for the new roles of vimentin in tissue repair and cellular growth.Mikrofilament, mikrotubuli och intermediära filament utgör cellens cytoskelett och formar ett komplext nätverk genom att interagera med cytoskelett-associerade proteiner. Cytoskelettet förser cellen med ett ramverk och reglerar olika cellulära funktioner. Intermediära filament utgör en stor proteinfamilj, som delats upp i olika grupper baserat på proteinets struktur och vävnadsuttryck. Vimentin är ett typ-III intermediärfilamentprotein, som uttrycks i stor grad i mesenkymala celler. Epitelceller genomgår epitelial-mesenkymal transition (EMT) under embryonalutvecklingen, vid sårläkning, cancer och fibros för att erhålla stamhet och en mer dynamisk och rörlig fenotyp. Vimentin är en välkänd EMT-markör, men dess roll i EMT är inte väl karaktäriserad. Detta examensarbete har undersökt vimentins roll i EMT under sårläkningsprocessen, vid celltillväxt och vid skydd mot oxidativ stress. I Vim-/- möss fördröjs sårläkningen till följd av defekter i EMT signaleringen, keratinocyt-migrationen, fibroblast-proliferationen och depositionen av kollagen. Medan vi kunde påvisa att vimentin är essentiell för funktionen av fibroblaster vid normal utveckling och sårläkning, vi observerade också att en avsaknad av vimentin reducerar fibroblasters storlek till följd av bristfällig mTOR signalering. Vimentin påverkar mTOR signalering genom att modulera aktiviteten av Rag GTPas, vilket i sin tur reglerar cellstorlek och autofagi. Vimentin stimulerar proliferation och skyddar cellerna mot oxidativ stress genom att upprätthålla redoxtillståndet. Vi har även påvisat att uttrycket av vimentin ökade i reglerande Treg celler, vilka kontrollerar immunresponsen och autoimmuna sjukdomar och detta förhöjda uttryck är medierat genom TGF-β1. Detta examensarbete påvisar nya roller för vimentin i vävnadsregenerering och celltillväxt

Social change and fertility transition in Sri Lanka

The study investigates and interprets the factors that contributed to the recent decline in fertility in Sri Lanka, despite its low economic standing. It seeks to elucidate the social transformation that has taken place and looks at the socio-cultural determinants that have brought about the process of fertility transition. In this regard, the significant effects of the welfare measures in force in the country in respect of health, education, nutrition and housing have been brought to light. Hence the study tends to fall outside the scope of the conventional wisdom laid down in the demographic transition theory outlined by Notestein, which emphasised the contribution that economic development plays in lowering fertility. The approach to the study hinges on selected variables like education, age at marriage, gender roles per se and female employment. The cardinal role played by free education in contributing to the transition is given particular coverage. Education is treated more as a cultural asset which determines and shapes values, preferences and aspirations in respect of marriage, fertility, family formation and other aspects such as career development which enables women to play roles away from home. Unfortunately, inferences about women's position do not always gain statistical support, as they are intricately woven into the fabric of societal gender settings and traditions. In respect of age at marriage, the socio-cultural factors of society like the caste system, a dowry and horoscope matching with details of Karmic determinants have been examined in some detail. The study also uncovers the social deprivation aspects which for long led women in the plantation sector to experience fertility performance lower than the national level. Going by normal demographic rationale, their high degree of labour force participation should account for it. But it was social deprivation and the resultant low nutritional levels that reduced their reproductive ability to low levels. With a better life ushered in by a programme of social uplift during the early 'eighties, this ethnic group showed signs of first a rise in fertility, and on having reached the threshold it has now begun showing signs of a decline attributable to healthier lives. Similarly, a relatively invisible agent, the prevalent “urban outlook," is shown to contribute to the transition process, and has recently become even more significant due to the intensive rural amelioration efforts of the government. This outlook is all pervasive and permeates the society in general in effecting the transition under review

1-Acetyl-c-3,t-3-dimethyl-r-2,c-6-diphenyl­piperidin-4-one

In the title compound, C21H23NO2, the piperidine ring adopts a distorted boat conformation. The two phenyl rings form dihedral angles of 64.6 (1) and 87.8 (1)° with the best plane through the piperidine ring. The crystal packing is governed by inter­molecular C—H⋯O inter­actions

Women in Development – Dissecting the Discourse

The concept of women’s development has now become an integral part of the development discourses and policy initiatives. This development has been informed by a remarkable though gradual shift in the perception about women, from the stature of victims and passive objects to that of independent agents. A significant impetus to raising such an informed platform came with the adoption of development issues within the UN system, in the background of increasing activism of development practitioners. The present paper critically traces the contours and its possible shades of this awakening that rises from the less ‘threatening’ planning for Women in Development (WID) to the more ‘confrontational’ gender planning with its aspiring goal of empowerment and emancipation. These movements have occasioned an increasing space for policy initiatives and interventions in favour of poor women in the Third World. There has been a gradual shift in orientation of these policy approaches towards women from ‘welfare’, to equity’ to anti-poverty’ to ‘efficiency’ and finally to ‘empowerment’. The policy reorientation reflects the changes in the basic economic approaches of the time, from modernization policies of accelerated growth, to basic needs strategies of growth with redistribution, to the recent so-called ‘compensatory measures’ for the neo-liberal illfare. The paper argues, inter alia, that the compensatory measures imply a substitution of the agency of civil society for that of the state in development process, the original agenda of the neo-liberalism.Women; Gender; Development; Equity; Empowerment

c-3,t-3-Dimethyl-r-2,c-7-diphenyl-1,4-diazepan-5-one

In the title compound, C19H22N2O, the diazepine ring adopts a distorted chair conformation. One of the N—H groups forms an inter­molecular N—H⋯O hydrogen bond generating an R 2 2(8) graph-set motif. The other N—H group does not form a hydrogen bond

c-3,t-3-Dimethyl-4-oxo-r-2,c-6-diphenyl­piperidine-1-carboxamide

In the title compound, C26H26N2O2, the piperidinone ring adopts a distorted boat conformation. The two phenyl rings substituted at positions 2 and 6 of the piperidinone ring occupy axial and equatorial orientations, which are approximately perpendicular to each other [89.14 (8)°]. The phenyl­carbamoyl group adopts an extended conformation. The crystal structure is stabilized by inter­molecular C—H⋯O inter­actions

1-Formyl-c-3,t-3-dimethyl-r-2,c-6-di­phenyl­piperidin-4-one

In the title compound, C20H21NO2, the piperidine ring adopts a distorted boat conformation. The phenyl rings substituted at the 2- and 6-positions of the piperidine ring subtend angles of 86.0 (1) and 67.3 (1)° with the mean plane of the piperidine ring (all six non-H atoms). The crystal packing features C—H⋯O inter­actions

r-2,c-6-Bis(4-methoxy­phenyl)-c-3,t-3-dimethyl-1-nitro­sopiperidin-4-one

In the title compound, C21H24N2O4, the piperidine ring adopts a distorted boat conformation. The crystal structure is stabilized by C—H⋯π inter­actions involving one of the methoxy­phenyl rings

c-3,t-3-Dimethyl-r-2,c-6-diphenyl­piperidin-4-one

In the title compound, C19H21NO, the piperidine ring adopts a chair conformation. The two phenyl rings attached to the piperidine ring at 2 and 6 positions occupy equatorial orientations and the dihedral angle between them is 57.53 (11)°. In the crystal, the mol­ecules are connected via weak inter­molecular C—H⋯π inter­actions, leading to a zigzag chains