Characterization of pip5k3 fleck corneal dystrophy-linked gene in zebrafish.

PIKfyve is a kinase encoded by pip5k3 involved in phosphatidylinositols (PdtIns) pathways. These lipids building cell membranes have structural functions and are involved in complex intracellular regulations. Mutations in human PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy [Li, S., Tiab, L., Jiao, X., Munier, F.L., Zografos, L., Frueh, B.E., Sergeev, Y., Smith, J., Rubin, B., Meallet, M.A., Forster, R.K., Hejtmancik, J.F., Schorderet, D.F., 2005. Mutations in PIP5K3 are associated with François-Neetens mouchetee fleck corneal dystrophy. Am. J. Hum. Genet. 77, 54-63]. We cloned the zebrafish pip5k3 and report its molecular characterization and expression pattern in adult fish as well as during development. The zebrafish PIKfyve was 70% similar to the human homologue. The gene encompassed 42 exons and presented four alternatively spliced variants. It had a widespread expression in the adult organs and was localized in specific cell types in the eye as the cornea, lens, ganglion cell layer, inner nuclear layer and outer limiting membrane. Pip5k3 transcripts were detected in early cleavage stage embryos. Then it was uniformly expressed at 10 somites, 18 somites and 24 hpf. Its expression was then restricted to the head region at 48 hpf, 72 hpf and 5 dpf and partial expression was found in somites at 72 hpf and 5 dpf. In situ on eye sections at 3 dpf showed a staining mainly in lens, outer limiting membrane, inner nuclear layer and ganglion cell layer. A similar expression pattern was found in the eye at 5 dpf. A temporal regulation of the spliced variants was observed at 1, 3 and 5 dpf and they were also found in the adult eye.

Phenotypic variability of retinocytomas: preregression and postregression growth patterns.

AIM: To describe the incidence of retinocytomas, their variability at presentation and their growth patterns both before and after regression.¦METHODS: Medical notes of the 525 patients of the Jules-Gonin Eye Hospital Retinoblastoma Clinic between 1964 and 2008 were reviewed and the charts of 36 patients with retinocytomas and/or phthisis bulbi were selected.¦RESULTS: The proportion of patients with retinocytomas and/or phthisis bulbi was 3.2%. The mean age at diagnosis was 28.7±17 years. Five tumours presented a cystic pattern (5.8%). Evidence of aggressive exophytic disease prior to spontaneous regression was documented in two eyes, and of invasive endophytic disease (regressed vitreous seeding or internal limiting membrane disruption) in three eyes. Twenty patients were followed with a mean follow-up of 44±60 months. Tumour growth was observed in 16% cases, benign cystic enlargement in 4% and malignant transformation in 12%.¦CONCLUSION: This large study of retinocytomas substantially expands the published features of retinocytoma by describing the cystic nature of some retinocytomas as well as clinical characteristics of the endophytic and exophytic preregression growth patterns. The authors report two different patterns of reactivation: benign cystic enlargement and malignant transformation with or without cystic growth. Higher than previously reported frequency of growth and possible life-threatening complications impose close lifetime follow-up of retinocytoma patients.

Early dyadic patterns of mother-infant interactions and outcomes of prematurity at 18 months.

OBJECTIVE: With the increased survival of very preterm infants, there is a growing concern for their developmental and socioemotional outcomes. The quality of the early mother-infant relationship has been noted as 1 of the factors that may exacerbate or soften the potentially adverse impact of preterm birth, particularly concerning the infant's later competencies and development. The first purpose of the study was to identify at 6 months of corrected age whether there were specific dyadic mother-infant patterns of interaction in preterm as compared with term mother-infant dyads. The second purpose was to examine the potential impact of these dyadic patterns on the infant's behavioral and developmental outcomes at 18 months of corrected age. METHODS: During a 12-month period (January-December 1998), all preterm infants who were <34 weeks of gestational age and hospitalized at the NICU of the Lausanne University Hospital were considered for inclusion in this longitudinal prospective follow-up study. Control healthy term infants were recruited during the same period from the maternity ward of our hospital. Mother-infant dyads with preterm infants (n = 47) and term infants (n = 25) were assessed at 6 months of corrected age during a mother-infant play interaction and coded according to the Care Index. This instrument evaluates the mother's interactional behavior according to 3 scales (sensitivity, control, and unresponsiveness) and the child's interactional behavior according to 4 scales (cooperation, compliance, difficult, and passivity). At 18 months, behavioral outcomes of the children were assessed on the basis of a semistructured interview of the mother, the Symptom Check List. The Symptom Check List explores 4 groups of behavioral symptoms: sleeping problems, eating problems, psychosomatic symptoms, and behavioral and emotional disorders. At the same age, developmental outcomes were evaluated using the Griffiths Developmental Scales. Five areas were evaluated: locomotor, personal-social, hearing and speech, eye-hand coordination, and performance. RESULTS: Among the possible dyadic patterns of interaction, 2 patterns emerge recurrently in mother-infant preterm dyads: a "cooperative pattern" with a sensitive mother and a cooperative-responsive infant (28%) and a "controlling pattern" with a controlling mother and a compulsive-compliant infant (28%). The remaining 44% form a heterogeneous group that gathers all of the other preterm dyads and is composed of 1 sensitive mother-passive infant; 10 controlling mothers with a cooperative, difficult, or passive infant; and 10 unresponsive mothers with a cooperative, difficult, or passive infant. Among the term control subjects, 68% of the dyads are categorized as cooperative pattern dyads, 12% as controlling pattern dyads, and the 20% remaining as heterogeneous dyads. At 18 months, preterm infants of cooperative pattern dyads have similar outcomes as the term control infants. Preterm infants of controlling pattern dyads have significantly fewer positive outcomes as compared with preterm infants of cooperative pattern dyads, as well as compared with term control infants. They display significantly more behavioral symptoms than term infants, including more eating problems than term infants as well as infants from cooperative preterm dyads. Infants of the controlling preterm dyads do not differ significantly for the total development quotient but have worse personal-social development than term infants and worse hearing-speech development than infants from cooperative preterm dyads. The preterm infants of the heterogeneous group have outcomes that can be considered as intermediate with no significant differences compared with preterm infants from the cooperative pattern or the controlling pattern dyads. CONCLUSION: Among mother-preterm infant dyads, we identified 2 specific patterns of interaction that could play either a protective (cooperative pattern) or a risk-precipitating (controlling pattern) role on developmental and behavioral outcome, independent of perinatal risk factors and of the family's socioeconomic background. The controlling pattern is much more prevalent among preterm than term dyads and is related to a less favorable infant outcome. However, the cooperative pattern still represents almost 30% of the preterm dyads, with infants' outcome comparable to the ones of term infants. These results point out the impact of the quality of mother-infant relationship on the infant's outcome. The most important clinical implication should be to support a healthy parent-infant relationship already in the NICU but also in the first months of the infant's life. Early individualized family-based interventions during neonatal hospitalization and transition to home have been shown to reduce maternal stress and depression and increase maternal self-esteem and to improve positive early parent-preterm infant interactions.

Geochemical study of vertebrate fossils from the Upper Cretaceous (Santonian) Csehbanya Formation (Hungary): Evidence for a freshwater habitat of mosasaurs and pycnodont fish

The diverse vertebrate remains from the Upper Cretaceous freshwater settings at Iharkut, Hungary, contain two fossil groups, Pycnodontiformes fish and Mosasauridae that are almost exclusively known from marine palaeo-environments. Hence, their appearance in alluvial sediments is very unusual. Trace element and isotope compositions of the remains have been analyzed to investigate the taphonomy and the ecological differences among the different fossil groups present at Iharkut. All examined fossils have undergone post-depositional diagenetic alteration, which resulted in high concentrations of REE, U, and Fe, together with almost complete homogenization of delta(18)O(CO3) values. Similar REE patterns in different fossils suggest a common origin for all remains, hence the discovered species most likely lived in the same local ecosystem. Despite partial diagenetic overprinting, the delta(18)O(PO4) values of the fossils indicate sufficient taxon-specific isotopic diversity to permit some broad conclusions on the palaeo-environment of the fossils. In particular, it is apparent that the isotopic composition of the Pycnodontiformes fish and Mosasauridae remains is most compatible with a freshwater palaeo-habitat and incompatible with a marine palaeo-environment. In addition, the Sr concentration and isotope data indicate that the Pycnodontiformes and Mosasauridae likely lived predominantly in a freshwater environment and were not simply occasional visitors to the Iharkut river ecosystem. Regarding other fossil groups, high delta(18)O(PO4) values of Alligatoroidea and Iharkutosuchus teeth suggest that these small crocodile species might have inhabited swamps and ponds where the water was relatively rich in (18)O due to evaporation. (c) 2009 Elsevier B.V. All rights reserved.

Cognitive and structural aspects of addiction: Relation between iris patterns, time perception, eyeblink rate, impulsivity and cigarette addiction

Objectif : Le but de ce travail est d'étudier les corrélations existantes entre les patterns de l'iris, la perception du temps et la fréquence de clignement des paupières (eye blink rate) et ceci en relation avec l'addiction à la cigarette. Méthodologie: Revue de la littérature existante. Expériences sur une cohorte d'au moins trente sujets fumeurs/non-fumeurs. Analyses statistiques. Résultats: Nos résultats confirment qu'il existe des relations entre l'impulsivité, les patterns d'iris, l'eye blink rate spontané et la perception du temps. Nous observons également que l'addiction à la cigarette et son niveau de dépendance ont une influence sur ces différentes mesures. En effet, les sujets fumeurs tendent à avoir une personnalité plus impulsive par rapport aux sujets contrôles. On remarque également une nette diminution de l'eye blink rate dans le groupe des fumeurs et une tendance à la sur-estimation du temps qui passe. Conclusion : Ce travail nous permet de mieux comprendre les différentes corrélations qui existent entre les différentes variables que nous avons mesurées (patterns d'iris, score d'impulsivité et eye blink rate) ainsi que leur relation à l'addiction à la cigarette. Dès lors qu'il est avéré que les fumeurs peuvent avoir une perception du temps altérée par rapport au groupe contrôle, il serait intéressant d'en étudier l'évolution sur le long terme (aggravation avec la durée du tabagisme actif) ainsi que les conséquences qui en découlent écologiquement au moyen d'études longitudinales et de terrain.

Patterns of oxygen consumption during establishment of cephalocaudal polarity in the early chick embryo.

Oxygen uptake was studied during the establishment of cephalocaudal polarity in the very early chick embryo, i.e., 10 hr before (stage VI) and at laying (stage X). Oxygen fluxes in minute regions of the intact blastoderms were measured in vitro by scanning microspectrophotometry in the presence or absence of glucose. The oxygen consumption of the whole blastoderm remained constant (6 nmol O2 X hr-1) throughout the period studied, although the number of cells increased more than twofold. The regional oxygen fluxes varied from 0.41 to 1.13 nmol O2 X hr-1 X mm-2 at stage VI and from 0.42 to 0.70 nmol O2 X hr-1 X mm-2 at stage X. At stage VI, the oxygen flux in the center of the blastoderm was significantly higher than that in its periphery. This pattern remained evident when the values were corrected for cell number or for cytoplasmic volume. At stage X, there was a tendency for the oxygen fluxes to decrease from the posterior to the anterior regions of the area pellucida. Thus the pattern of oxidative metabolism in the late uterine embryos seems to change from radial to bilateral. This change of symmetry probably reflects the process of formation of the embryonic axis. In addition, the fact that the oxygen uptake was similar in the presence or absence of glucose suggests that early chick embryos metabolize essentially intracellular stores.

First use of multiple substances: Identification of meaningful patterns

Context: Understanding the process through which adolescents and young adults are trying legal and illegal substances is a crucial point for the development of tailored prevention and treatment programs. However, patterns of substance first use can be very complex when multiple substances are considered, requiring reduction into a few meaningful number of categories. Data: We used data from a survey on adolescent and young adult health conducted in 2002 in Switzerland. Answers from 2212 subjects aged 19 and 20 were included. The first consumption ever of 10 substances (tobacco, cannabis, medicine to get high, sniff (volatile substances, and inhalants), ecstasy, GHB, LSD, cocaine, methadone, and heroin) was considered for a grand total of 516 different patterns. Methods: In a first step, automatic clustering was used to decrease the number of patterns to 50. Then, two groups of substance use experts, three social field workers, and three toxicologists and health professionals, were asked to reduce them into a maximum of 10 meaningful categories. Results: Classifications obtained through our methodology are of practical interest by revealing associations invisible to purely automatic algorithms. The article includes a detailed analysis of both final classifications, and a discussion on the advantages and limitations of our approach.

Discordances between phylogenetic and morphological patterns in alpine leaf beetles attest to an intricate biogeographic history of lineages in postglacial Europe.

Pleistocene glacial and interglacial periods have moulded the evolutionary history of European cold-adapted organisms. The role of the different mountain massifs has, however, not been accurately investigated in the case of high-altitude insect species. Here, we focus on three closely related species of non-flying leaf beetles of the genus Oreina (Coleoptera, Chrysomelidae), which are often found in sympatry within the mountain ranges of Europe. After showing that the species concept as currently applied does not match barcoding results, we show, based on more than 700 sequences from one nuclear and three mitochondrial genes, the role of biogeography in shaping the phylogenetic hypothesis. Dating the phylogeny using an insect molecular clock, we show that the earliest lineages diverged more than 1 Mya and that the main shift in diversification rate occurred between 0.36 and 0.18 Mya. By using a probabilistic approach on the parsimony-based dispersal/vicariance framework (MP-DIVA) as well as a direct likelihood method of state change optimization, we show that the Alps acted as a cross-roads with multiple events of dispersal to and reinvasion from neighbouring mountains. However, the relative importance of vicariance vs. dispersal events on the process of rapid diversification remains difficult to evaluate because of a bias towards overestimation of vicariance in the DIVA algorithm. Parallels are drawn with recent studies of cold-adapted species, although our study reveals novel patterns in diversity and genetic links between European mountains, and highlights the importance of neglected regions, such as the Jura and the Balkanic range.

Genome-wide patterns of latitudinal differentiation among populations of Drosophila melanogaster from North America.

Understanding the genetic underpinnings of adaptive change is a fundamental but largely unresolved problem in evolutionary biology. Drosophila melanogaster, an ancestrally tropical insect that has spread to temperate regions and become cosmopolitan, offers a powerful opportunity for identifying the molecular polymorphisms underlying clinal adaptation. Here, we use genome-wide next-generation sequencing of DNA pools ('pool-seq') from three populations collected along the North American east coast to examine patterns of latitudinal differentiation. Comparing the genomes of these populations is particularly interesting since they exhibit clinal variation in a number of important life history traits. We find extensive latitudinal differentiation, with many of the most strongly differentiated genes involved in major functional pathways such as the insulin/TOR, ecdysone, torso, EGFR, TGFβ/BMP, JAK/STAT, immunity and circadian rhythm pathways. We observe particularly strong differentiation on chromosome 3R, especially within the cosmopolitan inversion In(3R)Payne, which contains a large number of clinally varying genes. While much of the differentiation might be driven by clinal differences in the frequency of In(3R)P, we also identify genes that are likely independent of this inversion. Our results provide genome-wide evidence consistent with pervasive spatially variable selection acting on numerous loci and pathways along the well-known North American cline, with many candidates implicated in life history regulation and exhibiting parallel differentiation along the previously investigated Australian cline.

Are relationship patterns with significant others reenacted with the therapist?: a study of early transference reactions.

This study examines how patients' relationship patterns are reenacted with the therapist during the first sessions of psychotherapy. Forty (N = 40) outpatients treated with a Brief Psychodynamic Intervention were included in the study. Their narratives of relationship episodes with significant others (e.g., mother, father, romantic partner, colleagues) were compared with relationship episodes with their therapist using the Core Conflictual Relationship Theme method. The Core Conflictual Relationship Theme focuses on 3 aspects of patients' relationship narratives: what the patient wants from others or from self; how others react to his/her wish; and how the patient consequently reacts. Results showed that 60% of patients display similar relationship patterns with their therapist and with significant others. The patterns that were reenacted with the therapist were not the most pervasive ones but were similar to those found in relationship episodes involving parents or romantic partners. These findings provide some support for the clinical concept of repetition of internalized relational patterns with the therapist very early in psychotherapy. Clinical implications are discussed.

Conjugate eye deviation due to traumatic striatal-subthalamic lesion.

We report the case of a 22-year-old man after severe cranial trauma, who was noted to have conjugate eye deviation (CED) to the left. A magnetic resonance imaging (MRI) scan demonstrated a lesion in the left (ipsilateral) striatal-subthalamic region. The involvement of supranuclear fibres from the left frontal eye field (FEF) traveling to the right parapontine reticular formation (PPRF) could explain this clinical finding. Alternatively, involvement of deep brain nuclei, such as the striatum and the subthalamic nucleus, could be responsible for this phenomenon. This neurological presentation is unusual after severe cranial trauma.

Nutrition transition in a middle-income country: 22-year trends in the Seychelles.

BACKGROUND/OBJECTIVES: There is little objective information regarding nutrition transition in African countries. We assessed trends in nutrition patterns in the Seychelles between 1989 and 2011. SUBJECTS/METHODS: Population-based samples were obtained in 1989, 1994 and 2011 and participants aged 25-44 are considered in this study (n=493, 599 and 471, respectively). Similar, although not identical, food frequency questionnaires (FFQs) were used in each survey and the variables were collapsed into homogenous categories for the purpose of this study. RESULTS: Between 1989 and 2011, consumption frequency of fish (5+/week) decreased from 93 to 74%, whereas the following increased: meat (5+/week) 25 to 51%, fruits (1+/week) 48 to 94%, salty snacks (1+/week) 22 to 64% and sweet snacks (1+/week) 38 to 67% (P<0.001 for all). Consumption frequency decreased for home-brewed alcoholic drinks (1+/week) 16 to 1%, but increased for wine (1+/week) 5 to 33% (both P<0.001). Between 2004 and 2011, consumption frequency decreased for rice (2/day) 62 to 57% and tea (1+/day) 72 to 68%, increased for poultry (1+/week) 86 to 96% (all P<0.01), and did not change for vegetables (70.3 to 69.8%, P=0.65). CONCLUSIONS: Seychelles is experiencing nutrition transition characterized by a decreased consumption frequency of traditional staple foods (fish, polished rice), beverages (tea) and of inexpensive home brews, and increased consumption frequency of meat, poultry and snacks. Food patterns also became more varied along with a broader availability of products in the 22-year interval. The health impact of these changes should be further studied.