Sox4 participates in the modulation of Schwann cell myelination.

In order to identify new regulators of Schwann cell myelination potentially playing a role in peripheral nervous system (PNS) pathologies, we analysed gene expression profiling data from three mouse models of demyelinating neuropathies and from the developing PNS. This analysis revealed that Sox4, which encodes a member of the Sry-related high-mobility group box protein family, was consistently upregulated in all three analysed models of neuropathy. Moreover, Sox4 showed a peak in its expression during development that corresponded with the onset of myelination. To gain further insights into the role of Sox4 in PNS development, we generated a transgenic mouse that specifically overexpresses Sox4 in Schwann cells. Sox4 overexpression led to a temporary delay in PNS myelination without affecting axonal sorting. Importantly, we observed that, whereas Sox4 mRNA could be efficiently overexpressed, Sox4 protein expression in Schwann cells was strictly regulated. Finally, our data showed that enforced expression of Sox4 in the mouse model for Charcot-Marie-Tooth 4C aggravated its neuropathic phenotype. Together, these observations reveal that Sox4 contributes to the regulation of Schwann cell myelination, and also indicates its involvement in the pathophysiology of peripheral neuropathies.

Wavefront reconstruction by adding modulation capabilities of two liquid crystal devices

We analyze the behavior of complex information in the Fresnel domain, taking into account the limited capability to display complex values of liquid crystal devices when they are used as holographic displays. To do this analysis we study the reconstruction of Fresnel holograms at several distances using the different parts of the complex distribution. We also use the information adjusted with a method that combines two configurations of the devices in an adding architecture. The results of the error analysis show different behavior for the reconstructions when using the different methods. Simulated and experimental results are presented.

Assessment of the role of LASER-Doppler in the treatment of port-wine stains in infants.

BACKGROUND: Port-wine stains (PWS) are malformations of capillaries in 0.3% of newborn children. The treatment of choice is by pulsed dye LASER (PDL), and requires several sessions. The efficacy of this treatment is at present evaluated on the basis of clinical inspection and of digital photographs taken throughout the treatment. LASER-Doppler imaging (LDI) is a noninvasive method of imaging the perfusion of the tissues by the microcirculatory system (capillaries). The aim of this paper is to demonstrate that LDI allows a quantitative, numerical evaluation of the efficacy of the PDL treatment of PWS. METHOD: The PDL sessions were organized according to the usual scheme, every other month, from September 1, 2012, to September 30, 2013. LDI imaging was performed at the start and at the conclusion of the PDL treatment, and simultaneously on healthy skin in order to obtain reference values. The results evidenced by LDI were analyzed according to the "Wilcoxon signed-rank" test before and after each session, and in the intervals between the three PDL treatment sessions. RESULTS: Our prospective study is based on 20 new children. On average, the vascularization of the PWS was reduced by 56% after three laser sessions. Compared with healthy skin, initial vascularization of PWS was 62% higher than that of healthy skin at the start of treatment, and 6% higher after three sessions. During the 2 months between two sessions, vascularization of the capillary network increased by 27%. CONCLUSION: This study shows that LDI can demonstrate and measure the efficacy of PDL treatment of PWS in children. The figures obtained when measuring the results by LDI corroborate the clinical assessments and may allow us to refine, and perhaps even modify, our present use of PDL and thus improve the efficacy of the treatment.

Laser Doppler -vibrometrin käyttöönotto tärinämittauksissa

Tässä insinöörityössä otettiin käyttöön VTI Technologies Oy:lle hankittu laser Doppler - vibrometri, joka mittaa tärinää perustuen valon Dopplerin siirtymään. Työn tavoitteena oli perehtyä mittauslaitteistoon, muodostaa sille näytteenottolaitteisto ja käytännössä arvioida sen kyvykkyyttä mitata tärinää ja tuottaa uutta informaatiota. Työn teoreettisessa osuudessa perehdytään laser Doppler -vibrometrin teknologiaan ja toimintaperiaatteeseen sekä värähtelevien systeemien dynamiikkaan ja mallintamiseen. Työn käytännön osuuden suorittamiseksi perehdyttiin myös tärinätestauslaitteiston toimintaan, analogiasignaalin näytteenottoon sekä diskreettiin Fourier-muunnokseen perustuvaan signaalin spektrianalyysiin. Työssä käsitellään myös laser-mittauksen kohinalähteitä ja spektrianalyysin virhelähteitä. Työn käytännön osuudessa ohjelmoitiin Labview-mittausohjelmisto näytteenottolaitteistolle. Mittausohjelmistolla voidaan näytteistää vibrometrin mittaussignaalia ja muodostaa sen taajuusspektri. Mittauskohteita tässä työssä olivat kulmakiihtyvyystäryttimen mekaanisen liikkeen mittaus ja elementtikiekkosahan terän värähtelyjen mittaus. Mittaustulokset kulmakiihtyvyystäryttimestä osoittivat sen mekaanisen liikkeen säröytyvän voimakkaasti, johtuen todennäköisesti sen testialustan rakenteesta. Testialustan rakennetta tullaan kehittämään ja mittaukset toistetaan. Mittaustuloksiin elementtikiekkosahasta tuli suhtautua epäillen, koska mittaussignaalin intensiteetti oli erittäin heikko. Mittausten onnistuminen Laser Doppler -vibrometrillä edellyttää riittävää mittauskohteesta takaisinheijastuneen laser-valon intensiteettiä. Mittaustulokset osoittivat laser Doppler -vibrometrin olevan hyödyllinen työkalu tutkivassa tärinämittauksessa. Mittauskohteet, joiden pinta heijastaa huonosti valoa ja joihin ei voi asentaa erityistä heijastavaa teippiä, ovat kuitenkin haaste ja asettavat rajoituksen laser Doppler -vibrometrin käyttömahdollisuuksille. Tämän työn mittaustuloksia voidaan käyttää kulmakiihtyvyystäryttimen uusintamittausten vertailukohtana, kun arvioidaan kehitystyön onnistumista. Tätä työtä voidaan käyttää myös laser Doppler -vibrometrin ohjekirjana tärinämittauksissa.

Rotational Doppler effect in magnetic resonance

We compute the shift in the frequency of the spin resonance in a solid that rotates in the field of a circularly polarized electromagnetic wave. Electron-spin resonance, nuclear magnetic resonance, and ferromagnetic resonance are considered. We show that contrary to the case of the rotating LC circuit, the shift in the frequency of the spin resonance has strong dependence on the symmetry of the receiver. The shift due to rotation occurs only when rotational symmetry is broken by the anisotropy of the gyromagnetic tensor, by the shape of the body or by magnetocrystalline anisotropy. General expressions for the resonance frequency and power absorption are derived and implications for experiment are discussed.

Dual and Opposite Effects of hRAD51 Chemical Modulation on HIV-1 Integration.

The cellular DNA repair hRAD51 protein has been shown to restrict HIV-1 integration both in vitro and in vivo. To investigate its regulatory functions, we performed a pharmacological analysis of the retroviral integration modulation by hRAD51. We found that, in vitro, chemical activation of hRAD51 stimulates its integration inhibitory properties, whereas inhibition of hRAD51 decreases the integration restriction, indicating that the modulation of HIV-1 integration depends on the hRAD51 recombinase activity. Cellular analyses demonstrated that cells exhibiting high hRAD51 levels prior to de novo infection are more resistant to integration. On the other hand, when hRAD51 was activated during integration, cells were more permissive. Altogether, these data establish the functional link between hRAD51 activity and HIV-1 integration. Our results highlight the multiple and opposite effects of the recombinase during integration and provide new insights into the cellular regulation of HIV-1 replication.

Aspectos morfológicos e hemodinâmicos do baço em indivíduos normais: estudo por ultra-som Doppler

ANTECEDENTES: A diversidade de técnicas de mensuração esplênica pelo ultra-som Doppler (US Doppler), a falta de valores biométricos e dopplervelocimétricos dificultam a avaliação deste órgão e de suas características hemodinâmicas. OBJETIVO: Estabelecer padrões biométricos e hemodinâmicos por US-Doppler em indivíduos adultos sadios. MATERIAIS E MÉTODOS: Estudo prospectivo de 44 indivíduos sadios, sendo 19 do sexo masculino e 25 do sexo feminino, na faixa etária de 23 a 60 anos (37,4 ± 9,6). Morfometria (US modo-B): baço: eixos longitudinal (L), transversal (T) e ântero-posterior (AP); diâmetro da artéria esplênica (DAE) e diâmetro da veia esplênica (DVE). Índices morfométricos do baço: uniplanar (IBU), biplanar (IBB) e volume esplênico (VE). Dopplervelocimetria (US Doppler): a) artéria esplênica: velocidade de pico sistólico (VPS), média das velocidades máximas de fluxo (TAMax); índices de impedância vascular: índice de resistividade (IR); índice de pulsatilidade (IP); b) veia esplênica: média das velocidades máximas de fluxo (TAMax). RESULTADOS: Morfometria: L = 9,3 ± 1,3 cm; T= 3,9 ± 0,7 cm; AP = 8,4 ± 1,2 cm; DAE = 0,3 ± 0,07 cm; DVE: 0,5 ± 0,12 cm. Índices morfométricos do baço: IBU = 33,5 ± 9,9; IBB = 36,7 ± 10,3; VE = 164,3 ± 62,9 cm³. Dopplervelocimetria: a) artéria esplênica: VPS = 59,8 ± 23,6 cm/s; TAMax = 40,2 ± 15,9 cm/s; IP = 0,86 ± 0,30; IR = 0,55 ± 0,09; b) veia esplênica: TAMax = 16,8 ± 8,3 cm/s. CONCLUSÃO: Relato de valores biométricos e dopplervelocimétricos do baço em indivíduos sadios.

Estudo Doppler na hipertensão portal

A ultra-sonografia e o Doppler representaram grande marco no diagnóstico da hipertensão portal. Este fato decorre do aspecto não-invasivo destes métodos, possibilitando o estudo do fígado, do baço e da circulação esplâncnica. Neste artigo os autores discutem alguns aspectos importantes avaliados pela ultra-sonografia e pelo Doppler na avaliação da hipertensão portal.

Avaliação ultra-sonográfica e ao Doppler dos TIPS (anastomose portossistêmica intra-hepática transjugular)

A anastomose portossistêmica intra-hepática transjugular (TIPS) compreende a técnica mais recente e mais popular para o alívio da hipertensão portal sintomática, especialmente para os casos com varizes e hemorragia digestiva alta, e menos comumente para o tratamento da ascite refratária. Os TIPS podem apresentar complicações após sua colocação, como as estenoses e oclusões. A ultra-sonografia e o Doppler permitem o estudo dos TIPS de uma forma não invasiva. Neste artigo os autores relatam os achados recentes à ultra-sonografia e ao Doppler nos casos de funcionamento normal e anormal (estenoses/oclusões) dos TIPS.

Modulation de la douleur neuropathique par l'utilisation d'un vecteur viral adéno-associé recombinant et ARN interférent

Une lésion nerveuse périphérique est susceptible d'engendrer une douleur neuropathique caractérisée par des changements d'expression génique dans les neurones nociceptifs des ganglions spinaux. Parmi ces modifications, on note une augmentation transcriptionnelle du gène codant pour la guanosine triphosphate cyclohydrolase 1 (GCH1) considérée comme modulateur clé des douleurs neuropathiques périphériques1. La surexpression de la GCH1 induit alors une hausse de la concentration de la tétrahydrobiopterin (BH4), un cofacteur essentiel pour la production de catécholamines, de sérotonine et d'oxide nitrique dans les ganglions spinaux. La surexpression de ce cofacteur induit la production de ces neurotransmetteurs et contribue à l'augmentation de la sensibilité douloureuse. Dans ce travail, j'ai modulé l'expression de GCH1 par l'utilisation d'un vecteur viral adéno-associé. Tout d'abord, j'ai testé in vitro dans des cellules PC12 différentes molécules d'ARN interfèrent permettant la régulation négative de GCH1. Les cellules PC 12 contiennent constitutionnellement la GCH1 et sont donc intéressantes afin de tester et sélectionner un plasmide permettant une régulation négative efficace de cette molécule in vitro. Cela m'a permis de choisir après sélection de cellules par FACS et quantification protéique par Western blot les meilleurs sh-ARN à utiliser tant pour la régulation négative de GCH1 que pour le vecteur contrôle. J'ai ensuite co- transfecté ces plasmides avec le plasmide pDF6 dans des cellules HEK293T pour la production de mon vecteur viral (rAAV2/6) permettant la régulation négative de la GCH1 ainsi que de mon vecteur contrôle. Après avoir étudié deux voies d'injection chez le rat (dans le nerf sciatique et en intrathécal), j'ai retenu la voie intrathécale comme ayant le meilleur taux de transduction de mon vecteur viral au niveau des ganglions spinaux. Utiliser cette voie d'injection pour mon vecteur permet de cibler plus particulièrement les neurones nociceptifs des ganglions spinaux. J'ai ensuite étudié la modulation de la GCH1 et sa répercussion sur le développement et le maintien des douleurs neuropathiques dans le modèle animal « spared nerve injury » (SNI). Je n'ai pas obtenu de diminution de douleur ni au niveau comportemental ni au niveau moléculaire chez le rat. Ayant répété l'expérience chez la souris, j'ai obtenu une diminution significative de l'expression de la GCH1 au niveau de l'ARN messager. Je n'ai pas étudié l'efficacité de mon vecteur in vivo chez la souris car un autre groupe m'a devancé dans cette expérience et a publié une étude similaire montrant une régulation négative et efficace de la GCH1 sur les symptômes de douleur neuropathique. Mes résultats, associés à cette publication, démontrent la validité de mon hypothèse de départ et ouvrent de nouvelles perspectives thérapeutiques en prenant comme cible la production de BH4.