The function of Bmps and Runx2 in normal tooth development and in the pathogenesis of cleidocranial dysplasia

The development of many embryonic organs is regulated by reciprocal and sequential epithelial-mesenchymal interactions. These interactions are mediated by conserved signaling pathways that are reiteratively used. Cleidocranial dysplasia (CCD) is a congenital syndrome where both bone and tooth development is affected. The syndrome is characterized by short stature, abnormal clavicles, general bone dysplasia, and supernumerary teeth. CCD is caused by mutations in RUNX2, a transcription factor that is a key regulator of osteoblast differentiation and bone formation. The first aim of this study was to analyse the expression of a family of key signal molecules, Bone morphogenetic protein (Bmp) at different stages of tooth development. Bmps have a variety of functions and they were originally discovered as signals inducing ectopic bone formation. We performed a comparative in situ hybridisation analysis of the mRNA expression of Bmp2-7 from initiation of tooth development to differentiation of dental hard tissues. The expression patterns indicated that the Bmps signal between the epithelial and mesenchymal tissues during initiation and morphogenesis of tooth development, as well as during the differentiation of odontoblasts and ameloblasts. Furthermore, they are also part of the signalling networks whereby the enamel knot regulates the patterning of tooth cusps. The second aim was to study the role of Runx2 during tooth development and thereby to gain better understanding of the pathogenesis of the tooth phenotype in CCD. We analysed the tooth phenotype of Runx2 knockout mice and examined the patterns and regulation of Runx2 gene expression.. The teeth of wild-type and Runx2 mutant mice were compared by several methods including in situ hybridisation, tissue culture, bead implantation experiments, and epithelial-mesenchymal recombination studies. Phenotypic analysis of Runx2 -/- mutant tooth development showed that teeth failed to advance beyond the bud stage. Runx2 expression was restricted to dental mesenchyme between the bud and early bell stages of tooth development and it was regulated by epithelial signals, in particular Fgfs. We searched for downstream targets of Runx2 by comparative in situ hybridisation analysis. The expression of Fgf3 was downregulated in the mesenchyme of Runx2 -/- teeth. Shh expression was absent from the enamel knot in the lower molars of Runx2 -/- and reduced in the upper molars. In conclusion, these studies showed that Runx2 regulates key epithelial-mesenchymal interactions that control advancing tooth morphogenesis and histodifferentiation of the epithelial enamel organ. In addition, in the upper molars of Runx2 mutants extra buddings occured at the palatal side of the tooth bud. We suggest that Runx2 acts as an inhibitor of successional tooth formation by preventing advancing development of the buds. Accordingly, we propose that RUNX2 haploinsuffiency in humans causes incomplete inhibition of successional tooth formation and as a result supernumerary teeth.Sikiön ulkopintaa verhoavasta ektodermistä ja sen alaisesta mesenkyymistä kehittyy useita elimiä, joiden kehityksellä on paljon yhteisiä piirteitä. Ektodermaalisten elinten, kuten hampaiden ja rauhasten, solutyypit ja kehityksen anatomia on varsin samankaltaista kaikilla nisäkkäillä. Näiden elinten kehitystä säätelevät epiteelin ja mesenkyymin vuorovaikutukset, joihin osallistuvat yleisten viestiperheiden molekyylit. Pään ja kasvojen luut muodostuvat hermostopienasta peräisin olevasta ektomesenkyymistä. Niiden kehitys tapahtuu ns. välittömän luutumisen mekanismilla eli intramembranoottisesti, kun muut luut muodostuvat rustoisen välivaiheen kautta eli endokondraalisesti. Hampaille ja luille on yhteistä mineralisoituneen kovakudoksen muodostus. Viestimolekyylejä koodaavien geenien mutaatiot aiheuttavat lukuisia kehityshäiriöitä hampaissa ja pään alueen luissa. Kleidokraniaalinen dysplasia on oireyhtymä, jossa on muutoksia sekä luissa että hampaissa. Oireyhtymään liittyy häiriintynyt pituuskasvu, yleinen luiden poikkeavuus, solisluiden epämuodostumat ja ylilukuiset hampaat. Kleidokraniaalisen dysplasian aiheuttaa mutaatio RUNX2 geenissä, joka on välttämätön luusolujen erilaistumiselle. Väitöskirjatyön ensimmäinen tavoite oli tutkia luun morfogeenisten kasvutekijöiden (Bmp) funktiota hampaan kehityksessä. Bmp:t löydettiin alunperin niiden luuta indusoivan kyvyn perusteella, mutta niillä on lisäksi lukuisia funktioita eri elinten kehityksessä. Bmp2, -3, -4, -5, -6, ja -7 geenien ilmentyminen paikannettiin kehittyvissä hiiren hampaissa. Tulokset viittaavat siihen, että Bmp:t välittävät epiteelin ja mesenkyymin välisiä vuorovaikutuksia sekä hampaan kehityksen alkuvaiheissa että hampaan kovakudoksia muodostavien solujen erilaistumisen aikana. Lisäksi Bmp:t ovat osana hampaan signaalikeskuksen, kiillekyhmyn, signaaliverkostossa, joka säätelee hampaan kaavoittumisen. Toinen tavoite oli tutkia Runx2 geenin funktiota hampaan kehityksessä ja siten myös paremmin ymmärtää kleidokraniaalisen dysplasian patogeneesi ja molekyläärinen tausta. Ensin tutkittiin Runx2 geenin ilmentymistä hampaan kehityksen aikana ja todettiin, että ilmentyminen rajautuu hampaan mesenkyymiin silmuvaiheesta varhaiseen kellovaiheeseen. Lisäksi tutkittiin Runx2 poistogeenisten hiirten hampaiden kehitystä ja todettiin, että kehitys pysähtyy silmuvaiheseen. Runx2:n säätelemiä geenejä etsittiin vertailemalla viestiverkostojen geenien ilmenemistä Runx2 poistogeenisella ja normaalilla hiirellä hampaiden kehityksen aikana . Runx2 poistogeenisen hiiren hampaissa todettiin fibroblastikasvutekijäperheeseen kuuluvan Fgf3:n ilmentymisen olevan hyvin alhainen ja lisäksi Shh geenin ilmentymisen puuttuvan alamolaareissa ja vähentyneen ylämolaareista. Tulokset osoittivat, että Runx2 säätelee epiteelin ja mesenkyymin välisiä vuorovaikutuksia, jotka ohjaavat hampaan varhaista kehitystä. Lisäksi havaitsimme ylimääräisiä silmuja Runx2 poistogeenisen hiiren ylämolaareissa ja esitimme että Runx2 estää ylilukuisten hampaiden muodostumista. Tähän viittaa myös se, että yhden Runx2 alleelin puuttuminen kleidokraanialista dysplasiaa sairastavilla potilailla aiheuttaa ylilukuisia hampaita

What do conferences do? What is academics’ intangible return on investment (ROI) from attending an academic tourism conference?

This is a submitted of an article published by Taylor & Francis in the JOURNAL OF TEACHING IN TRAVEL & TOURISM on December 2017, available online: http://www.tandfonline.com/10.1080/15313220.2017.1407517Conferences are funny events. They are self-evident elements of our lives as academics: meetings that occur, often annually; take place in various locations; and involve (hopefully) like-minded people, aiming to share their latest research findings. Conferences are actually so self-evident that very little research exists analysing what takes place at conferences, why people attend them in the first place, and essentially what the conference does to delegates as participants. This article is, on one hand, a reflective report from an academic conference: TEFI 9—Celebrating the Disruptive Power of Caring in Tourism Education. But it is also simultaneously an analysis of the implicit and explicit rationale and return on investment for attending academic conferences, in the words of three, at that time, PhD candidate rapporteurs and one professor rapporteur, who acts as this article’s narrator.submittedVersio

Exact Coupling Coefficient Distribution in the Doorway Mechanism

In many--body and other systems, the physics situation often allows one to interpret certain, distinct states by means of a simple picture. In this interpretation, the distinct states are not eigenstates of the full Hamiltonian. Hence, there is an interaction which makes the distinct states act as doorways into background states which are modeled statistically. The crucial quantities are the overlaps between the eigenstates of the full Hamiltonian and the doorway states, that is, the coupling coefficients occuring in the expansion of true eigenstates in the simple model basis. Recently, the distribution of the maximum coupling coefficients was introduced as a new, highly sensitive statistical observable. In the particularly important regime of weak interactions, this distribution is very well approximated by the fidelity distribution, defined as the distribution of the overlap between the doorway states with interaction and without interaction. Using a random matrix model, we calculate the latter distribution exactly for regular and chaotic background states in the cases of preserved and fully broken time--reversal invariance. We also perform numerical simulations and find excellent agreement with our analytical results.Comment: 22 pages, 4 figure

On the role of shake-off in single-photon double ionization

The role of shake-off for double ionization of atoms by a single photon with finite energy has become the subject of debate. In this letter, we attempt to clarify the meaning of shake-off at low photon energies by comparing different formulations appearing in the literature and by suggesting a working definition. Moreover, we elaborate on the foundation and justification of a mixed quantum-classical ansatz for the calculation of single-photon double ionization

Thermodynamics of SmCo5 compound doped with Fe and Ni: An ab initio study

SmCo5 permanent magnets exhibit enormous uniaxial magnetocrystalline anisotropy energy and have a high Curie temperature. However, their low energy product is a significant deficiency. To increase the energy product in SmCo5, we propose substituting cobalt with iron, that has a much larger magnetic moment, in a SmCoNiFe3 magnet where nickel is used as a thermodynamic stabilizer

Many-body approach to proton emission and the role of spectroscopic factors

The process of proton emission from nuclei is studied by utilizing the two-potential approach of Gurvitz and Kalbermann in the context of the full many-body problem. A time-dependent approach is used for calculating the decay width. Starting from an initial many-body quasi-stationary state, we employ the Feshbach projection operator approach and reduce the formalism to an effective one-body problem. We show that the decay width can be expressed in terms of a one-body matrix element multiplied by a normalization factor. We demonstrate that the traditional interpretation of this normalization as the square root of a spectroscopic factor is only valid for one particular choice of projection operator. This causes no problem for the calculation of the decay width in a consistent microscopic approach, but it leads to ambiguities in the interpretation of experimental results. In particular, spectroscopic factors extracted from a comparison of the measured decay width with a calculated single-particle width may be affected.Comment: 17 pages, Revte

Red-Emitting Manganese-doped Aluminum Nitride Phosphor

We report high efficiency luminescence with a manganese-doped aluminum nitride red-emitting phosphor under 254 nm excitation, as well as its excellent lumen maintenance in fluorescent lamp conditions, making it a candidate replacement for the widely deployed europium-doped yttria red phosphor. Solid-state reaction of aluminum nitride powders with manganese metal at 1900 °C, 10 atm N2 in a reducing environment results in nitrogen deficiency, as revealed diffuse reflectance spectra. When these powders are subsequently annealed in flowing nitrogen at 1650 °C, higher nitrogen content is recovered, resulting in white powders. Silicon was added to samples as an oxygen getter to improve emission efficiency. NEXAFS spectra and DFT calculations indicate that the Mn dopant is divalent. From DFT calculations, the UV absorption band is proposed to be due to an aluminum vacancy coupled with oxygen impurity dopants, and Mn2+ is assumed to be closely associated with this site. In contrast with some previous reports, we find that the highest quantum efficiency with 254 nm excitation (Q.E. = 0.86 ± 0.14) is obtained in aluminum nitride with a low manganese doping level of 0.06 mol.%. The principal Mn2+ decay of 1.25 ms is assigned to non-interacting Mn sites, while additional components in the microsecond range appear with higher Mn doping, consistent with Mn clustering and resultant exchange coupling. Slower components are present in samples with low Mn doping, as well as strong afterglow, assigned to trapping on shallow traps followed by detrapping and subsequent trapping on Mn

VISA – Communication monitoring and assessment system of the Finnish Government : Government Communication Project 2007

Published by the Prime Minister's Office.Peer reviewe

Theoretical description of deformed proton emitters: nonadiabatic coupled-channel method

The newly developed nonadiabatic method based on the coupled-channel Schroedinger equation with Gamow states is used to study the phenomenon of proton radioactivity. The new method, adopting the weak coupling regime of the particle-plus-rotor model, allows for the inclusion of excitations in the daughter nucleus. This can lead to rather different predictions for lifetimes and branching ratios as compared to the standard adiabatic approximation corresponding to the strong coupling scheme. Calculations are performed for several experimentally seen, non-spherical nuclei beyond the proton dripline. By comparing theory and experiment, we are able to characterize the angular momentum content of the observed narrow resonance.Comment: 12 pages including 10 figure