Evidences of the cooperative role of the chemokines CCL3, CCL4 and CCL5 and its receptors CCR1+and CCR5+in RANKL+ cell migration throughout experimental periodontitis in mice

Periodontal disease (PD) is characterized by the inflammatory bone resorption in response to the bacterial challenge, in a host response that involves a series of chemokines supposed to control cell influx into periodontal tissues and determine disease outcome. In this study, we investigated the role of chemokines and its receptors in the immunoregulation of experimental PD in mice. Aggregatibacter actinomycetemcomitans-infected C57BI/6 (WT) mice developed an intense inflammatory reaction and severe alveolar bone resorption, associated with a high expression of CCL3 and the migration of CCR5+, CCR1+ and RANKL+ cells to periodontal tissues. However, CCL3KO-infected mice developed a similar disease phenotype than WT strain, characterized by the similar expression of cytokines (TNF-alpha, IFN-gamma and IL-10), osteoclastogenic factors (RANKL and OPG) and MMPs (MMP-1, MMP-2, MMP-3, TIMP-1 and TIMP-3), and similar patterns of CCR1+, CCR5+ and RANKL+ cell migration. The apparent lack of function for CCL3 is possible due the relative redundancy of chemokine system, since chemokines such as CCL4 and CCL5, which share the receptors CCR1 and CCR5 with CCL3, present a similar kinetics of expression than CCL3. Accordingly, CCL4 and CCL5 kinetics of expression after experimental periodontal infection remain unaltered regardless the presence/absence of CCL3. Conversely, the individual absence of CCR1 and CCR5 resulted in a decrease of leukocyte infiltration and alveolar bone loss. When CCR1 and CCR5 were simultaneously inhibited by met-RANTES treatment a significantly more effective attenuation of periodontitis progression was verified, associated with lower values of bone loss and decreased counts of leukocytes in periodontal tissues. Our results suggest that the absence of CCL3 does not affect the development of experimental PD in mice, probably due to the presence of homologous chemokines CCL4 and CCL5 that overcome the absence of this chemokine. In addition, our data demonstrate that the absence of chemokine receptors CCR1+ and CCR5+ attenuate of inflammatory bone resorption. Finally, our data shows data the simultaneous blockade of CCR1 and CCR5 with MetRANTEs presents a more pronounced effect in the arrest of disease progression, demonstrating the cooperative role of such receptors in the inflammatory bone resorption process throughout experimental PD. (C) 2009 Elsevier Inc. All rights reserved.

The geodiamolide H, derived from Brazilian sponge Geodia corticostylifera, regulates actin cytoskeleton, migration and invasion of breast cancer cells cultured in three-dimensional environment

We are investigating effects of the depsipeptide geodiamolide H, isolated from the Brazilian sponge Geodia corticostylifera, on cancer cell lines grown in 3D environment. As shown previously geodiamolide H disrupts actin cytoskeleton in both sea urchin eggs and breast cancer cell monolayers. We used a normal mammary epithelial cell line MCF 10A that in 3D assay results formation of polarized spheroids. We also used cell lines derived from breast tumors with different degrees of differentiation: MCF7 positive for estrogen receptor and the Hs578T, negative for hormone receptors. Cells were placed on top of Matrigel. Spheroids obtained from these cultures were treated with geodiamolide H. Control and treated samples were analyzed by light and confocal microscopy. Geodiamolide H dramatically affected the poorly differentiated and aggressive Hs578T cell line. The peptide reverted HsS78T malignant phenotype to polarized spheroid-like structures. MCF7 cells treated by geodiamolide H exhibited polarization compared to controls. Geodiamolide H induced striking phenotypic modifications in Hs578T cell line and disruption of actin cytoskeleton. We investigated effects of geodiamolide H on migration and invasion of Hs578T cells. Time-lapse microscopy showed that the peptide inhibited migration of these cells in a dose-dependent manner. Furthermore invasion assays revealed that geodiamolide H induced a 30% decrease on invasive behavior of Hs578T cells. Our results suggest that geodiamolide H inhibits migration and invasion of Hs578T cells probably through modifications in actin cytoskeleton. The fact that normal cell lines were not affected by treatment with geodiamolide H stimulates new studies towards therapeutic use for this peptide.

3D Cell-Migration Studies using Two-Photon Engineered Polymer Scaffolds

We use two-photon polymerization to fabricate 3D scaffolds with precise control over pore size and shape for studying cell migration in 3D. These scaffolds allow movement of cells in all directions. The fabrication, imaging, and quantitative analysis method developed here can be used to do systematic cell studies in 3D.

Synthesis of the Macrolactone of Migrastatin and Analogues with Potent Cell-Migration Inhibitory Activity

The synthesis of the macrolactone core of migrastatin 2, its potent anti-metastasis analogue 34, and ester derivatives 35 and 38 are reported. The approach involves the use of a dihydroxylation reaction to establish the desired C-8 stereocenter followed by a metathesis cyclization reaction. The effects of the compounds on the migration and invasion of human breast cancer cells were evaluated by using the wound-healing and the Boyden-chamber cell-migration and cell-invasion assays. The results revealed a high potency of the macrolactones 2 and 34 and the ester analogues 35 and 38, which suggests they have potential as antimetastatic agents.

The Sphene-Centered Ocellar Texture: An Effect of Grain-Supported Flow and Melt Migration in a Hyperdense Magma Mush

The sphene-centered ocellar texture consists of leucocratic ocelli with sphene (titanite) crystals at the center, enclosed in a biotite-rich matrix. This texture has been recognized worldwide in hybrid intermediate rocks. On the basis of structural, petrological, and geochronological data from selected outcrops of the Variscan Ribadelago pluton (NW Iberian Massif), we propose that the ocelli were formed by migration and accumulation of a residual melt through a plagioclase- and biotite-dominated crystalline framework. At the late stage of crystallization, the magma acted as a hyperdense suspension and reacted to the pressure gradient caused by the regional stress field, entering the domain of grain-supported flow. Microstructures reveal that aligned crystal domains arose in the crystal framework from the shearing and compaction of the crystal mush and behaved as magmatic microshears. Relative displacement of adjacent crystal clusters along these microshears corresponded to the onset of Reynolds dilatancy that generated an expansion of the crystal mush, involving melt migration and pore aperture. The mineralogy of the ocelli, dominated by andesine and sphene, represents the composition of the migrating melt. The chemistry of this late, Ti-rich melt stems from the incongruent melting of biotite. Magmatic sphene from the ocelli yields a U-Pb age of 317 +/- 1 Ma, which represents the final crystallization of the hybridized magmatic system. Moreover, this texture offers an opportunity to better understand the rheological behavior of highly crystallized magmas.

Glypican-3 regulates migration, adhesion and actin cytoskeleton organization in mammary tumor cells through Wnt signaling modulation

Glypican-3 (GPC3) is a proteoglycan involved in migration, proliferation and cell survival modulation in several tissues. There are many reports demonstrating a downregulation of GPC3 expression in some human tumors, including mesothelioma, ovarian and breast cancer. Previously, we determined that GPC3 reexpression in the murine mammary adenocarcinoma LM3 cells induced an impairment of their in vivo invasive and metastatic capacities together with a higher susceptibility to in vitro apoptosis. Currently, the signaling mechanism of GPC3 is not clear. First, it was speculated that GPC3 regulates the insulin-like growth factor (IGF) signaling system. This hypothesis, however, has been strongly challenged. Recently, several reports indicated that at least in some cell types GPC3 serves as a selective regulator of Wnt signaling. Here we provide new data demonstrating that GPC3 regulates Wnt pathway in the metastatic adenocarcinoma mammary LM3 cell line. We found that GPC3 is able to inhibit canonical Wnt signals involved in cell proliferation and survival, as well as it is able to activate non canonical pathway, which directs cell morphology and migration. This is the first report indicating that breast tumor cell malignant properties can be reverted, at least in part, by GPC3 modulation of Wnt signaling. Our results are consistent with the potential role of GPC3 as a metastasis suppressor.

Intrachain Energy Migration to Weak Charge-Transfer State in Polyfluorene End-Capped with Naphthalimide Derivative

Polyfluorene end-capped with N-(2-benzothiazole)-1 8-naphthalimide (PF-BNI) is a highly fluorescent material with fluorescence emission modulated by solvent polarity Its low energy excited state is assigned as a mixed configuration state between the singlet S(1) of the fluorene backbone (F) with the charge transfer (CI) of the end group BNI The triexponential fluorescence decays of PF-BNI were associated with fast energy migration to form an intrachain charge-transfer (ICCT) state polyfluorene backbone decay and ICCT deactivation Time-resolved fluorescence anisotropy exhibited biexponential relaxation with a fast component of 12-16 ps in addition to a slow one in the range 0 8-1 4 ns depending on the solvent showing that depolarization occurs from two different processes energy migration to form the ICCT state and slow rotational diffusion motion of end segments at a longer time Results from femtosecond transient absorption measurements agreed with anisotropy decay and showed a decay component of about 16 ps at 605 nm in PF BNI ascribed to the conversion of S(1) to the ICCT excited state From the ratio of asymptotic and initial amplitudes of the transient absorption measurement the efficiency of intrachain ICCT formation is estimated in 0 5 which means that on average, half of the excited state formed in a BNI-(F)(n)-BNI chain with n = 32 is converted to its low energy intrachain charge-transfer (ICCT) state

Cloud computing - Moving to the cloud

Cloud computing innebär användning av datorresurser som är tillgängliga via ett nätverk, oftast Internet och är ett område som har vuxit fram i snabb takt under de senaste åren. Allt fler företag migrerar hela eller delar av sin verksamhet till molnet. Sogeti i Borlänge har behov av att migrera sina utvecklingsmiljöer till en molntjänst då drift och underhåll av dessa är kostsamma och tidsödande. Som Microsoftpartners vill Sogeti använda Microsoft tjänst för cloud computing, Windows Azure, för detta syfte. Migration till molnet är ett nytt område för Sogeti och de har inga beskrivningar för hur en sådan process går till. Vårt uppdrag var att utveckla ett tillvägagångssätt för migration av en IT-lösning till molnet. En del av uppdraget blev då att kartlägga cloud computing, dess beståndsdelar samt vilka för- och nackdelar som finns, vilket har gjort att vi har fått grundläggande kunskap i ämnet. För att utveckla ett tillvägagångssätt för migration har vi utfört flera migrationer av virtuella maskiner till Windows Azure och utifrån dessa migrationer, litteraturstudier och intervjuer dragit slutsatser som mynnat ut i ett generellt tillvägagångssätt för migration till molnet. Resultatet har visat att det är svårt att göra en generell men samtidigt detaljerad beskrivning över ett tillvägagångssätt för migration, då scenariot ser olika ut beroende på vad som ska migreras och vilken typ av molntjänst som används. Vi har dock utifrån våra erfarenheter från våra migrationer, tillsammans med litteraturstudier, dokumentstudier och intervjuer lyft vår kunskap till en generell nivå. Från denna kunskap har vi sammanställt ett generellt tillvägagångssätt med större fokus på de förberedande aktiviteter som en organisation bör genomföra innan migration. Våra studier har även resulterat i en fördjupad beskrivning av cloud computing. I vår studie har vi inte sett att någon tidigare har beskrivit kritiska framgångsfaktorer i samband med cloud computing. I vårt empiriska arbete har vi dock identifierat tre kritiska framgångsfaktorer för cloud computing och i och med detta täckt upp en del av kunskapsgapet där emellan.

Organisationer, ojämlikhet, migration : förändringar av den etniska arbetsdelningen i svensk byggnadssektor

Organizations, Inequality, Migration – Changes of the Ethnic Division of Labour in the Swedish Construction Sector During the 1990s the number of migrants from Eastern Europe increased in the Swedish construction sector. This article examines how this change was initiated by changes in the organizational population in the construction sector. The gradual enlargement of the European Union changed the institutional framework for organizations in Sweden. This created increased opportunities for new organizational forms in the construction sector. The specific niche of the new organizations was to recruit and hire out workers from Eastern Europe that were paid lower wages than Swedish workers. The diffusion of this organizational form contributed to a change of norms and beliefs about what was legitimate and illegitimate when employing migrants. This implies that the inequalities that this organizational form introduces have gained increased legitimacy in Sweden. Or in other words, it has become increasingly socially acceptable to pay migrants lower wages than Swedish workers

Growth, migration and unemployment across Swedish municipalities

Fundamental questions in economics are why some regions are richer than others, why their economic growth rates vary, whether their growth tends to converge and the key factors that contribute to the variations. These questions have not yet been fully addressed, but changes in the local tax base are clearly influenced by the average income growth rate, net migration rate, and changes in unemployment rates. Thus, the main aim of this paper is to explore in depth the interactive effects of these factors (and local policy variables) in Swedish municipalities, by estimating a proposed three-equation system. Our main finding is that increases in local public expenditures and income taxes have negative effects on subsequent local income growth. In addition, our results support the conditional convergence hypothesis, i.e. that average income tends to grow more rapidly in relatively poor local jurisdictions than in initially “richer” jurisdictions, conditional on the other explanatory variables.

Violence and reproductive health preceding flight from war : accounts from Somali born women in Sweden

Background: Political violence and war are push factors for migration and social determinants of health among migrants. Somali migration to Sweden has increased threefold since 2004, and now comprises refugees with more than 20 years of war experiences. Health is influenced by earlier life experiences with adverse sexual and reproductive health, violence, and mental distress being linked. Adverse pregnancy outcomes are reported among Somali born refugees in high-income countries. The aim of this study was to explore experiences and perceptions on war, violence, and reproductive health before migration among Somali born women in Sweden. Method: Qualitative semi-structured individual interviews were conducted with 17 Somali born refugee women of fertile age living in Sweden. Thematic analysis was applied. Results: Before migration, widespread war-related violence in the community had created fear, separation, and interruption in daily life in Somalia, and power based restrictions limited access to reproductive health services. The lack of justice and support for women exposed to non-partner sexual violence or intimate partner violence reinforced the risk of shame, stigmatization, and silence. Social networks, stoicism, and faith constituted survival strategies in the context of war. Conclusions: Several factors reinforced non-disclosure of violence exposure among the Somali born women before migration. Therefore, violence-related illness might be overlooked in the health care system. Survival strategies shaped by war contain resources for resilience and enhancement of well-being and sexual and reproductive health and rights in receiving countries after migration.

Kulturella aspekters betydelse i vårdkontakter ur afrikanska kvinnors perspektiv vid migration- en litteraturöversikt

Bakgrund: Ungefär 16,5 procent av Sveriges befolkning är idag födda i ett annat land än Sverige. Under de senaste åren har invandringen till Sverige ökat med 12 procent av vilka 55,419 är kvinnor. De flesta av dessa kvinnor är ursprungligen från Afrika, merparten från Somalia. Många av dessa kvinnor talar varken svenska eller engelska och det förekommer stora kulturella skillnader från den svenska kulturen, vilket leder till svårigheter för dessa kvinnor i mötet med hälso- sjukvården. Syfte: Syftet var att sammanställa aktuell forskning som belyser kulturella aspekters betydelse i vårdkontakter ur afrikanska kvinnors perspektiv vid migration. Metod: En litteraturstudie. Resultat: Två huvudkategorier och åtta underkategorier identifierades. Resultatet visade att tidigare erfarenheter inverkade på nuvarande vård, samt att det fanns hinder för kommunikation mellan kvinnorna och hälso- sjukvårdspersonal i form av att kvinnorna känner att de inte kan säga allt inför en tolk, speciellt inte om tolken var manlig eller inte igenkänd. Tolkning av familj och vänner kunde påverka att vissa saker inte översattes och att känsliga ämnen påverkade översättaren. Slutsats: Det framkom att det finns kulturella aspekter som har betydelse i vårdkontakten och det innebär att det finns behov av mer medvetenhet av kulturella aspekter i mötet med afrikanska kvinnor.

Understanding the "black box" of a health-promotion program : keys to enable health among older persons aging in the context of migration

Although the need to make health services more accessible to persons who have migrated has been identified, knowledge about health-promotion programs (HPPs) from the perspective of older persons born abroad is lacking. This study explores the design experiences and content implemented in an adapted version of a group-based HPP developed in a researcher-community partnership. Fourteen persons aged 70-83 years or older who had migrated to Sweden from Finland or the Balkan Peninsula were included. A grounded theory approach guided the data collection and analysis. The findings showed how participants and personnel jointly helped raise awareness. The participants experienced three key processes that could open doors to awareness: enabling community, providing opportunities to understand and be understood, and confirming human values and abilities. Depending on how the HPP content and design are being shaped by the group, the key processes could both inhibit or encourage opening doors to awareness. Therefore, this study provides key insights into how to enable health by deepening the understanding of how the exchange of health-promoting messages is experienced to be facilitated or hindered. This study adds to the scientific knowledge base of how the design and content of HPP may support and recognize the capabilities of persons aging in the context of migration.