A multi-contrast MRI study of microstructural brain damage in patients with mild cognitive impairment.

OBJECTIVES: The aim of this study was to investigate pathological mechanisms underlying brain tissue alterations in mild cognitive impairment (MCI) using multi-contrast 3 T magnetic resonance imaging (MRI). METHODS: Forty-two MCI patients and 77 healthy controls (HC) underwent T1/T2* relaxometry as well as Magnetization Transfer (MT) MRI. Between-groups comparisons in MRI metrics were performed using permutation-based tests. Using MRI data, a generalized linear model (GLM) was computed to predict clinical performance and a support-vector machine (SVM) classification was used to classify MCI and HC subjects. RESULTS: Multi-parametric MRI data showed microstructural brain alterations in MCI patients vs HC that might be interpreted as: (i) a broad loss of myelin/cellular proteins and tissue microstructure in the hippocampus (p ≤ 0.01) and global white matter (p < 0.05); and (ii) iron accumulation in the pallidus nucleus (p ≤ 0.05). MRI metrics accurately predicted memory and executive performances in patients (p ≤ 0.005). SVM classification reached an accuracy of 75% to separate MCI and HC, and performed best using both volumes and T1/T2*/MT metrics. CONCLUSION: Multi-contrast MRI appears to be a promising approach to infer pathophysiological mechanisms leading to brain tissue alterations in MCI. Likewise, parametric MRI data provide powerful correlates of cognitive deficits and improve automatic disease classification based on morphometric features.

CARACTERIZAÇÃO AGRONÔMICA E DIVERGÊNCIA GENÉTICA ENTRE ACESSOS DE ABACAXIZEIRO NAS CONDIÇÕES DO ESTADO DE MATO GROSSO

RESUMO Para iniciar um programa de melhoramento genético, a existência da variabilidade genética é essencial. Assim, a caracterização dos genótipos é o primeiro passo para adefinição da estratégia de melhoramento a ser adotada. Neste sentido, este trabalho teve como objetivo estudar a divergência genética, com base em caracteres morfoagronômicos, entre 19 acessos de abacaxizeiro (vAnanas comosusar. comosus) pertencentes à coleção ativa de trabalho da UNEMAT de Tangará da Serra (MT). Foram utilizados 52 descritores, sendo 31 descritores qualitativos e 21 quantitativos. Para aanálise dos dados, utilizou-se do coeficiente de coincidência simples, da distância euclidiana média padronizada e da análise conjunta por meio da distância de Gower. Pelos descritores avaliados, verificou-se amplavariabilidade entre os acessos de A. comosus var. comosus. A análise conjunta foi mais eficiente na representação da variabilidade genética entre os acessos avaliados. Sugerem-se os cruzamentos dos acessos 4; 5; 6; 7; 8; 13 e 19 com os acessos 3; 9; 10 e 11.

Older persons' perceptions of general practitioner or specialist primary care physicians : same point of view? : older persons' primary care perception

La perception du patient vis-à-vis de son médecin traitant (MT) a suscité beaucoup de recherches et d'interet, notamment à cause de l'importance de la relation médecin-patient nécessaire à la qualité des soins. En Suisse, dans un contexte de libre choix du médecin, le rôle de MT peut être assumé par un generalise mais aussi, théoriquement, par un spécialiste. La fréquence de cette situation est cependant inconnue de même que son impact sur l'expérience des patients. L'objectif principal de cette etude était de décrire l'expérience des personnes âgées du canton de Vaud auprès de leur medecin traitant et de tester l'hypothèse selon laquelle cette expérience serait différente lorsque le MT est décrit comme « Généraliste » (MT Gén) ou comme « Spécialiste » (MT Spéc). Méthode : La recherche a été effectuée sur la base des données d'une enquête par questionnaire, envoyé à la population lausannoise participant à l'étude Lc65+ et à un échantillon supplémentaire de personnes agees de 68 ans ou plus sélectionnées aléatoirement dans le canton de Vaud. L'analyse a porté sur 17 items relatifs à la perception qu'ont les patients de leur MT, regroupés en 4 thèmes ? Access,bihte/Disponibilité, Relation Médecin-Patient, Information et Continuité des soins Nous ayons également analysé le recours déclaré aux soins ambulatoires, aux consultations de services d urgence, ainsi qu'aux actes de prévention. Les différences de perception et de recours selon le type de MT (Gen vs Spéc) ont été analysées par des modèles multivariés tenant compte de l'âge du sexe de I education, de la morbidité, de la présence de symptômes dépressifs et de la durée de la relation medecin-patient. Résultats : Les participants ont exprimé une perception favorable de leur MT à des taux excédant 75% pour la plupart des 17 items. Cependant, seulement 38 à 51% des participants ont répondu positivement aux questions relatives à la disponibilité en dehors des heures d'ouvertures, à l'accès au MT le soir ou en tin de semaine, à la possibilité de visites à domicile, à la probabilité de se voir prescrire des medicaments coûteux en cas de besoin, ou à la connaissance du médecin des médicaments en vente libre que le patient consomme. Les analyses bivariées et multivariées n'ont pas montré de différence entre les groupes MT Gén et MT Spec quant à la perception qu'ont les patients de leur MT, au recours aux actes de prévention ou aux services de santé. Conclusion : L'expérience des personnes interrogées était globalement positive, à part quelques questions concernant principalement le thème de l'Accessibilité/Disponibilité du MT. Nous n'avons pas mis en evidence de différence de perception ou de recours aux soins entre les deux groupes que nous avons analyses pour tester notre hypothèse. Perspective : Cette étude connaît des limites (données rapportées par les participants, groupe des MT Spéc de taille restreinte, absence de données sur les non-répondants, possible conflit de loyauté vis-à-vis du MT pour certaines questions) mais repose sur un large échantillon lui conférant une puissance suffisante, aléatoirement sélectionné dans une population géographiquement définie. Bien que ces résultats ne soient généralisables qu'au canton de Vaud, elle montre d'abord que les spécialistes reconnus comme MT s'inscrivent généralement dans des disciplines impliquant une formation en medec.ne interne. Dans cette circonstance, elle ne met en évidence aucune différence de résultats entre les personnes âgées traitées par un MT généraliste ou spécialiste.

The role of geography and ecology in shaping repeated patterns of morphological and genetic differentiation between European minnows (Phoxinus phoxinus) from the Pyrenees and the Alps

Neutral and selective processes c an drive repeated patterns of evolu tion in dif ferent groups of populationsexp eriencing similar ecol ogica l gradients. In this paper, we used a combinat ion of nucl ear and mitochondrialDNA markers, as well as geometric morphometrics, to investigate repeated patterns of morphological andgenetic divergence of E uropean minnows in two mountain ranges : the Pyrenees and the Al ps. Europeanminnows (Phoxinus phoxinus) are cyprinid fish i nha bitin g most freshwater bodies in Europe, including those indifferent mountain r anges that could act as major geographical barriers to gene flow. We explored patterns ofP. phoxinus phenotypic and genetic di versi fication along a gradi ent of alti tude common to the two mountainranges, and tested for isolation by distance (IBD), isolation by environment (IBE) and isolation by adaptation(IBA). The results indicated that populations from the Pyr enees a nd the Alps bel ong to two well differentiated,reciprocally monophyletic mt DNA lineages. Substantial genetic differentiation due to geographical isolationwithin and between populations from the Pyrenees and the Alps was also found using rapidly evolving AFLPsmarkers (isolation by distance or IBD), as well as morphological differences between mountain ranges. Als o,morphology varied strong ly with elevation and so did genetic differentiation to a lower extent. Despitemoderate evidence for IBE and IBA, and therefore of repeated evolution, substantial population heterogeneitywas found at the genetic level, suggesting that selection and population specific genetic drift act in concert toaffect genetic divergence.

Planarians as a model to assess in vivo the role of matrix metalloproteinase genes during homeostasis and regeneration

Matrix metalloproteinases (MMPs) are major executors of extracellular matrix remodeling and, consequently, play key roles in the response of cells to their microenvironment. The experimentally accessible stem cell population and the robust regenerative capabilities of planarians offer an ideal model to study how modulation of the proteolytic system in the extracellular environment affects cell behavior in vivo. Genome-wide identification of Schmidtea mediterranea MMPs reveals that planarians possess four mmp-like genes. Two of them (mmp1 and mmp2) are strongly expressed in a subset of secretory cells and encode putative matrilysins. The other genes (mt-mmpA and mt-mmpB) are widely expressed in postmitotic cells and appear structurally related to membrane-type MMPs. These genes are conserved in the planarian Dugesia japonica. Here we explore the role of the planarian mmp genes by RNA interference (RNAi) during tissue homeostasis and regeneration. Our analyses identify essential functions for two of them. Following inhibition of mmp1 planarians display dramatic disruption of tissues architecture and significant decrease in cell death. These results suggest that mmp1 controls tissue turnover, modulating survival of postmitotic cells. Unexpectedly, the ability to regenerate is unaffected by mmp1(RNAi). Silencing of mt-mmpA alters tissue integrity and delays blastema growth, without affecting proliferation of stem cells. Our data support the possibility that the activity of this protease modulates cell migration and regulates anoikis, with a consequent pivotal role in tissue homeostasis and regeneration. Our data provide evidence of the involvement of specific MMPs in tissue homeostasis and regeneration and demonstrate that the behavior of planarian stem cells is critically dependent on the microenvironment surrounding these cells. Studying MMPs function in the planarian model provides evidence on how individual proteases work in vivo in adult tissues. These results have high potential to generate significant information for development of regenerative and anti cancer therapies.

Dietary calcium restriction enhances cadmium-induced metallothionein synthesis in rats.

Experiments were conducted with adult male rats to investigate the effects of dietary calcium (Ca) restriction upon intake and tissue distribution of cadmium (Cd), and Cd-metallothionein (Mt) synthesis. Four groups of animals were fed either a low-Ca, semisynthetic diet (0.1% Ca) or the same diet supplemented with 0.8% Ca (normal diet). The caloric intake was similar in all groups. Two groups (low-Ca and normal diet) were used as controls, and two groups (low-Ca and normal diet) received 100 mg/l Cd (as CdCl2) in drinking water. Cd levels in liver, kidney, spleen and red cells were measured in all animals after 8 weeks of treatment. Concomitantly, Mt levels in plasma, liver and kidney were evaluated by radioimmunoassay. Ca deficiency entailed marked and significant increases in accumulation of Cd and synthesis of Mt in all assayed tissues. It is concluded that dietary Ca restriction, independent of caloric intake, enhances Cd intestinal absorption and tissue accumulation, which is followed by increased tissue Mt synthesis.

Cadmium uptake and induction of metallothionein synthesis in a renal epithelial cell line (LLC-PK1).

LLC-PK1 cells, an established cell line from pig kidney with proximal tubule properties, were cultivated in vitro at confluence on plastic dishes. They were then exposed (apical side) to inorganic cadmium (CdCl2, 5 microM) for periods ranging between 1 to 24 h. Analysis of the cell supernatant after homogenisation and ultracentrifugation indicated that Cd taken up in the first 3 h was bound to cytosolic high molecular weight proteins, but was redistributed to low molecular weight proteins at later stages. Induction of Cd-metallothionein (Cd-Mt) synthesis, as judged from Cd-Mt binding to a specific anti-Cd-Mt antibody and from the rate of 35S-cys incorporation into a specific protein fraction, was apparent 3-6 h after the addition of Cd to the incubation medium.

Fate of cadmium in rat renal tubules: a microinjection study.

109Cd was injected into the lumen of superficial proximal or distal tubules of rat kidneys, and recovery in the pelvic urine from the ipsilateral kidney was measured. Fractional recovery of labeled inulin always exceeded 90%. About 70% of injected inorganic Cd (CdCl2) was taken up by the epithelium of proximal tubules, while more than 90% of the injected amount was recovered after distal microinjection. The proximal fractional Cd uptake of a 1:1 (molar) Cd-L-cysteine complex was 82%, but was below 60% for a 5-10:1 molar ratio of cysteine:Cd. The chelate Cd-pentetic acid was recovered in final urine nearly quantitatively after proximal or distal microinjection. Fractional uptake of 109Cd from a Cd-metallothionein (Mt) complex, following proximal microinjection, ranged between 17 (Cd-Mt 0.19 mM) and 8% (Cd-Mt 1.5 mM). It is concluded that luminal Cd uptake by the tubular epithelium depends markedly on the chemical form of Cd and, when present, occurs mostly or exclusively in proximal tubules.

Interventions présumées des scribes concernant le motif de l'arbre sacré dans le Pentateuque

Abstract: This article deals with several presumed scribal interventions which all concern the sacred tree motif. One finds deliberate changes in the MT, in the Septuagint, in Targum Onkelos and in the Vulgate. The Greek translators of Genesis and Samuel (1-2 Kingdoms) avoided rendering the word אשׁל "tamarisk" by its equivalent μυρίκη, chosing instead the word ἄρουρα "field". Similarly, the Greek translator of Genesis, in the passage of the death of Rebecca's nurse Deborah, passed over the motif of her burial under a grand tree. According to the hypothesis of the present article, all four changes are related to one other; they might be due to the translator's fear to connect the respective texts with traditions and customs concerning the Egyptian god Osiris. On the other side, a scribe of the proto-Massoretic tradition modified the readings mentioning the large tree of Mamre close to Hebron. By changing the noun's number from singular to plural the corrector tried to conceal the existence and importance of the sacred tree in the tradition of Abraham. By contrast, the scribe did not modify texts related to the sacred tree of Shechem. This disparity of treatment may be explained by the fact that, in the view of the Judean scribe, the tree of Shechem would put the Samaritans in a bad light. Finally, the authors of Targum Onkelos and of the Vulgate intervened almost systematically in Pentateuchal texts having the terms אֵלוֹן) אלון or אַלּוֹן ), which always designate a holy tree. The two expressions are rendered by terms referring to plains (Targum Onkelos) or a valley (Vulgate).

Characterisation of anatomical properties of the human basal ganglia using magnetic resonance imaging

The detailed in-vivo characterization of subcortical brain structures is essential not only to understand the basic organizational principles of the healthy brain but also for the study of the involvement of the basal ganglia in brain disorders. The particular tissue properties of basal ganglia - most importantly their high iron content, strongly affect the contrast of magnetic resonance imaging (MRI) images, hampering the accurate automated assessment of these regions. This technical challenge explains the substantial controversy in the literature about the magnitude, directionality and neurobiological interpretation of basal ganglia structural changes estimated from MRI and computational anatomy techniques. My scientific project addresses the pertinent need for accurate automated delineation of basal ganglia using two complementary strategies: ? Empirical testing of the utility of novel imaging protocols to provide superior contrast in the basal ganglia and to quantify brain tissue properties; ? Improvement of the algorithms for the reliable automated detection of basal ganglia and thalamus Previous research demonstrated that MRI protocols based on magnetization transfer (MT) saturation maps provide optimal grey-white matter contrast in subcortical structures compared with the widely used Tl-weighted (Tlw) images (Helms et al., 2009). Under the assumption of a direct impact of brain tissue properties on MR contrast my first study addressed the question of the mechanisms underlying the regional specificities effect of the basal ganglia. I used established whole-brain voxel-based methods to test for grey matter volume differences between MT and Tlw imaging protocols with an emphasis on subcortical structures. I applied a regression model to explain the observed grey matter differences from the regionally specific impact of brain tissue properties on the MR contrast. The results of my first project prompted further methodological developments to create adequate priors for the basal ganglia and thalamus allowing optimal automated delineation of these structures in a probabilistic tissue classification framework. I established a standardized workflow for manual labelling of the basal ganglia, thalamus and cerebellar dentate to create new tissue probability maps from quantitative MR maps featuring optimal grey-white matter contrast in subcortical areas. The validation step of the new tissue priors included a comparison of the classification performance with the existing probability maps. In my third project I continued investigating the factors impacting automated brain tissue classification that result in interpretational shortcomings when using Tlw MRI data in the framework of computational anatomy. While the intensity in Tlw images is predominantly

Mitotic regulation by Polo-like kinase 1 and the Chromosomal Passenger Complex

During mitosis, the duplicated genome must be accurately divided between two daughter cells. Polo-like kinase 1 (Plk1) and Aurora B kinase, together with its binding partners Incenp, Survivin and Borealin (chromosomal passenger complex, CPC), have key roles in coordinating mitotic events. The accuracy of cell division is safeguarded by a signaling cascade termed the mitotic spindle checkpoint (SC), which ensures that chromosomes are not physically separated before correct bipolar attachments have been formed between kinetochores and spindle microtubules (MT). An inhibitory “wait anaphase” signal, which delays chromosome separation (anaphase onset), is created at individual kinetochores and broadcasted throughout the cell in response to lack of kinetochore-microtubule (kMT) attachment or proper interkinetochore tension. It is believed that the fast turnover of SC molecules at kinetochores contributes to the cell’s ability to produce this signal and enables rapid responses to changing cellular conditions. Kinetochores that lack MT attachment and tension express a certain phosphoepitope called the 3F3/2 phosphoepitope, which has been linked to SC signaling. In the experimental part, we investigated the regulation of the 3F3/2 phosphoepitope, analyzed whether CPC molecules turn over at centromeres, and dissected the mitotic roles of the CPC using a microinjection technique that allowed precise temporal control over its function. We found that the kinetochore 3F3/2 phosphoepitope is created by Plk1, and that CPC proteins exhibit constant exchange at centromeres. Moreover, we found that CPC function is necessary in the regulation of chromatid movements and spindle morphology in anaphase. In summary, we identified new functions of key mitotic regulators Plk1 and CPC, and provided insighs into the coordination of mitotic events.

Investigaciones en Teotihuacan: redefiniendo los viejos problemas

Teotihuacan se encuentra en el sector noroeste de la Cuenca de México (19' 34'N, 99VO'W) entre los 2.240 y 3.100 mt s.n.m. Es una de las culturas de la Antigüedad más asombrosas; no tan sólo por el tamaño de sus pirámides y estructura habitacionales sino porque supone el desarrollo de un fenómeno urbano extremadamente complejo que marcará el desarrollo del periodo Clásico en el Altiplano mexicano a lo largo de setecientos años de historia humana. La arqueología teotihuacana es engañosamente poco complicada. Teotihuacan se encuentra en un área accesible y por varias razones en las que se mezclan aspectos culturales, económicos (es una de las zonas arqueológicas más visitadas del mundo) y también políticos ha gozado de proyectos de investigación más o menos continuados desde hace un siglo. Para el investigador foráneo, el primer impacto se deriva del tamaño y volumen de las estructuras y de la cantidad de material arqueológico que puede derivarse de cualquier excavación en esta zona. A nivel de trabajo de campo, y en comparación con otras culturas de la Antigüedad los teotihuacanos tenían una arquitectura muy bien definida con una traza urbana bien reticulada

Rule-based machine translation between Bulgarian and Macedonian

This paper describes the development of a two-way shallow-transfer rule-based machine translation system between Bulgarian and Macedonian. It gives an account of the resources and the methods used for constructing the system, including the development of monolingual and bilingual dictionaries, syntactic transfer rules and constraint grammars. An evaluation of thesystem's performance was carried out and compared to another commercially available MT system for the two languages. Some future work was suggested.

Variação anual do rendimento e composição química dos componentes voláteis da Siparuna guianensis Aublet

This work describes the volatile composition obtained by hidrodistillation of fresh leaves of Siparuna guianensis Aublet collected from Cuiabá (MT), Brazil. The composition of DCM extract of hydrolate was determined by GC-MS analysis and the results showed that the specie present a range of components according to their phenology and period of the leaves were collects. The highest volatile components yield was obtained during the reproductive period and the principal compound was the siparunone.