Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling.

Conformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of α2β1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, α2E336A, in the α2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin. Full FAK activation was observed, since phosphorylation was not only confirmed in residue Y397, but also in residues Y576/7. Furthermore, initiation of downstream signaling by paxillin phosphorylation in residue Y118 was evident, even though this activation was transient by nature, probably due to the lack of talin involvement in FAK activation and the absence of vinculin in the adhesion complexes formed by the nonactivated integrins. Altogether these results indicate that the nonactivated integrins can induce cellular signaling, but the outcome of the signaling differs from conventional integrin signaling

Sikiökö lainsuojaton? Raskaana olevan päihteitä käyttävän naisen tahdosta riippumattoman hoidon oikeudelliset edellytykset ja syntyvän lapsen oikeudellinen asema

Raskaudenaikaisen päihteiden käytön on todettu vahingoittavan sikiön terveyttä ja kehitystä erittäin vakavasti, pahimmassa tapauksessa aiheuttamalla syntyvälle lapselle elinikäisiä vammoja. Suomessa äitiensä päihteiden käytön haittavaikutuksille altistuu vuosittain arviolta 3000 sikiötä. Jopa 6 prosenttia raskaana olevista naisista kärsii päihderiippuvuudesta. Voimassa olevan oikeuden mukaan vielä syntymättömän lapsen terveysvaara ei kuitenkaan ole hyväksyttävä peruste raskaana olevan naisen tahdosta riippumattomaan hoitoon määräämiselle tilanteessa, jossa äiti tietoisena raskaudestaan jatkaa päihteiden käyttöä eikä näin ollen kykene edesauttamaan lapsensa mahdollisuutta kehitykseen ja terveeseen elämään. Tutkimuksessa selvitetään syntyvän lapsen oikeudellista asemaa siitä näkökulmasta, voitaisiinko lapsen terveyden suojeluun vedoten oikeuttaa ääritapauksissa raskaana olevan naisen perusoikeuksien rajoittaminen tahdosta riippumattomalla päihdehoidolla. Oikeudellinen ongelma kulminoituu siihen, millä perusteilla raskaana olevan päihteitä käyttävän naisen itsemääräämisoikeutta voidaan rajoittaa, mikäli henkilö ei tahdo tai pysty raitistumaan raskaana ollessaan, eikä vapaaehtoinen hoito siten tule kyseeseen. Tutkimuksessa selvitetään, millaisissa tilanteissa sikiötä suojellaan nykylainsäädännössä, ja voisiko suojaamistarkoitusta laajentaa koskemaan myös tutkimuskysymyksen tilannetta. Pohdintaa edellyttää sen seikan arvioiminen, voisiko raskaana olevan naisen oman terveyden vaarantuminenkin edellyttää suojelua julkisen vallan toimenpitein. Syntyvän lapsen kasvun ja kehityksen turvaamiseksi päihdehuoltolakia tulisi uudistaa siten, että raskaana olevien päihdeongelmaisten naisten tahdosta riippumaton hoito olisi mahdollista syntyvän lapsen terveysvaaran perusteella. Oikeudellisesti merkittäväksi ongelma muodostuu se, että vielä syntymättömän lapsen ei ole katsottu olevan oikeussubjekti, perusoikeuksien haltija, vaan täysimääräinen perusoikeussuoja alkaa vasta syntymän hetkellä. Näin ollen lapsella ei voi olla ehdotonta oikeutta syntyä, joka oikeuttaisi naisen itsemääräämisoikeuden rajoittamisen. Syntymätöntä ihmiselämää on kuitenkin haluttu suojata vetoamalla valtiosäännön perusperiaatteista ihmisarvon loukkaamattomuuteen, jonka perusteella lääketieteelliset ja tieteelliset kokeilut on kielletty ja asetettu aikarajoja abortille. Ihmisarvon loukkaamattomuudella on näin ollen tiettyä itsenäistä oikeudellista vaikutusta, josta voidaan johtaa syntyvän lapsen suojaamisen tarve yhdessä raskaana olevan päihdeongelmaisen naisen alentuneen itsemääräämiskyvyn perusteella. Syntyvän lapsen ja äidin terveyden suojelu yhteisenä intressinä edellyttää itsemääräämisoikeuden rajoittamisen perustelua valtiosääntöoikeudellisesti kestävällä tavalla perusoikeuksien yleisten rajoitusedellytysten vaatimukset täyttäen

Tutkimusta historia- ja yhteiskuntatieteiden välissä – tieteidenvälisyyden kohtaaminen, haasteet ja tulevaisuus

The article discusses interdisciplinarity from a theoretical and historical point of view. The problemacy arises from the writer’s personal experience and connects to her dissertation project, in which she aims to study the Finnish university-environment relationships both from a historical and sociological perspective. The first part of the article addresses the topics of differentiation of the scientific disciplines, conceptualisation of the relationships between the disciplines and the phenomena of scientific identities and cultures. The second part presents an overview of narrativity and theory in history and sociology and the role of these two disciplines as social sciences and sciences in society. In the closing paragraph the author discusses the present state and future of scientific disciplines in a society, which increasingly stresses cooperation between different disciplines in societal problem solving.Artikkeli käsittelee tieteidenvälisyyttä tieteenteoreettisesta ja historiallisesta näkökulmasta. Erityisesti tarkasteluun nousee historiatieteen ja sosiologian välinen suhde. Artikkelin erityisteemoja ovat tieteidenvälisyyden käsitteellistäminen, tieteenalaidentiteetit ja -kulttuurit. Lopuksi artikkelissa pohditaan tieteenalojen merkitystä ja tulevaisuutta yhteiskunnallisessa kontekstissa

Genetic admixture and language shift in the medieval Volga-Oka interfluve

Peer reviewe

Nuclear translocation of vitellogenin in the honey bee (Apis mellifera)

Vitellogenin (Vg) is a conserved protein used by nearly all oviparous animals to produce eggs. It is also pleiotropic and performs functions in oxidative stress resistance, immunity, and, in honey bees, behavioral development of the worker caste. It has remained enigmatic how Vg affects multiple traits. Here, we asked whether Vg enters the nucleus and acts via DNA-binding. We used cell fractionation, immunohistology, and cell culture to show that a structural subunit of honey bee Vg translocates into cell nuclei. We then demonstrated Vg-DNA binding theoretically and empirically with prediction software and chromatin immunoprecipitation with sequencing (ChIP-seq), finding binding sites at genes influencing immunity and behavior. Finally, we investigated the immunological and enzymatic conditions affecting Vg cleavage and nuclear translocation and constructed a 3D structural model. Our data are the first to show Vg in the nucleus and suggest a new fundamental regulatory role for this ubiquitous protein.Peer reviewe

Serum neutrophil gelatinase-associated lipocalin and recovery of kidney graft function after transplantation

Peer reviewe

Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling

Conformational activation of integrins is generally required for ligand binding and cellular signalling. However, we have previously reported that the nonactivated conformation of alpha 2 beta 1 integrin can also bind to large ligands, such as human echovirus 1. In this study, we show that the interaction between the nonactivated integrin and a ligand resulted in the activation of focal adhesion kinase (FAK) in a protein kinase C dependent manner. A loss-of-function mutation, alpha 2E336A, in the alpha 2-integrin did not prevent the activation of FAK, nor did EDTA-mediated inactivation of the integrin. Full FAK activation was observed, since phosphorylation was not only confirmed in residue Y397, but also in residues Y576/7. Furthermore, initiation of downstream signaling by paxillin phosphorylation in residue Y118 was evident, even though this activation was transient by nature, probably due to the lack of talin involvement in FAK activation and the absence of vinculin in the adhesion complexes formed by the nonactivated integrins. Altogether these results indicate that the nonactivated integrins can induce cellular signaling, but the outcome of the signaling differs from conventional integrin signaling

The PIM1 kinase promotes prostate cancer cell migration and adhesion via multiple signalling pathways

The ability of cells to migrate and form metastases is one of the fatal hallmarks of cancer that can be conquered only with better understanding of the molecules and regulatory mechanisms involved. The oncogenic PIM kinases have been shown to support cancer cell survival and motility, but the PIM-regulated pathways stimulating cell migration and invasion are less well characterized than those affecting cell survival. Here we have identified the glycogen synthase kinase 3 beta (GSK3B) and the forkhead box P3 (FOXP3) transcription factor as direct PIM targets, whose tumour-suppressive effects in prostate cancer cells are inhibited by PIM-induced phosphorylation, resulting in increased cell migration. Targeting GSK3B is also essential for the observed PIM-enhanced expression of the prostaglandin-endoperoxide synthase 2 (PTGS2), which is an important regulator of both cell migration and adhesion. Accordingly, selective inhibition of PIM activity not only reduces cell migration, but also affects integrin-mediated cell adhesion. Taken together, these data provide novel mechanistic insights on how and why patients with metastatic prostate cancer may benefit from therapies targeting PIM kinases, and how such approaches may also be applicable to inflammatory conditions</p

Estudo comparativo entre os métodos de estimativa visual e goniometria para avaliação das amplitudes de movimento da articulação do ombro

Objetivo: comparar a utilização das técnicas de estimativa visual e de goniometria para medidas de amplitudes de movimento (ADM´s) do ombro (elevação, extensão, abdução e rotações externa/interna a 90° de abdução) e indicar o melhor procedimento e referência para medidas das ADM’s da articulação do ombro. Métodos: dois profissionais da área de saúde com diferentes experiências na avaliação de ADM’s avaliaram noventa e sete indivíduos normais de ambos os sexos com idade entre 20 a 50 anos, utilizando os métodos de estimativa visual recomendados pela American Academy Orthopaedic Surgeons (AAOS) e o método de goniometria recomendado por Norkin e White (1997). Comparações entre os métodos apresentaram diferenças significativas para todos os movimentos. Conclusões: existem diferenças entre os valores das ADM’s do ombro avaliadas pelo método de estimativa visual da AAOS e os valores obtidos pela goniometria, sugerindo que a goniometria é até o momento, o melhor método para avaliar diferenças discretas entre as medidas.Objective: to compare the use of the the goniometer and of visual estimatation to measure the range of motion (ROM) of the shoulder joint (elevation, extension, abduction, and external/ internal rotation at 90° of abduction), and to indicate the best procedure and reference measures of the ROM of the shoulder. Méthods: two professionals of the area of health with different experiences in the evaluation of the ROM evaluated 97 normal individuals of both sexes aged between 20 to 50 years, using the method of visual estimation recommended by the American Academy Orthopaedic Surgeons (AAOS) and the goniometric method of Norkin and White (1997). Conclusions: comparisons between the methods resulted in significant differences for all movements. The results of this study demonstrated that differences exist between the values of ROM of the shoulder evaluated by visual estimate of AAOS and values obtained by the goniometer, suggesting that the goniometer is still the best method to evaluate discrete differences in ROM