Cytotoxic effects of FGF2-saporin on bovine epithelial lens cells in vitro.

PURPOSE: To test the ability of two preparations of FGF2-saporin, either FGF2 chemically conjugated to saporin (FGF2-SAP) or genetically engineered FGF2-saporin (rFGF2-SAP) to inhibit the growth of bovine epithelial lens (BEL) cells in vitro when in solution and when immobilized on heparin surface-modified (HSM) polymethylmethacrylate (PMMA) intraocular lenses (IOLs). METHOD: Bovine epithelial lens cells were incubated with various concentrations FGF2-saporin for as long as 4 days. The number of surviving cells was determined by counting the number of nuclei. Because FGF2 binds to heparin, FGF2-saporin was incubated with HSM PMMA IOLs; excess toxin was washed off, and the BEL cells were grown on the FGF2-saporin-treated IOLs (HSM and non-HSM) for 4 days. Cell density was determined by image analysis. RESULTS: Both FGF2-SAP and rFGF2-SAP were highly cytotoxic (nM range), with rFGF2-SAP 10 times less active than FGF2-SAP. FGF2-saporin bound to the surface of HSM IOLs and eluted by 2M NaCl retained its activity. Toxin bound to HSM IOLs killed more than 90% of the BEL cells placed on the IOL surface within 4 days. The ability of FGF2-saporin to prevent the growth of cells on the IOL surface was strictly dependent on the presence of heparin on the IOL. CONCLUSIONS: FGF2-saporin is bound to HSM PMMA IOLs and prevents the growth of epithelial cells on the surface of the lens.

Fate of rubrospinal neurons after unilateral section of the cervical spinal cord in adult macaque monkeys: effects of an antibody treatment neutralizing Nogo-A.

The present study describes in primates the effects of a spinal cord injury on the number and size of the neurons in the magnocellular part of the red nucleus (RNm), the origin of the rubrospinal tract, and evaluates whether a neutralization of Nogo-A reduces the lesioned-induced degenerative processes observed in RNm. Two groups of monkeys were subjected to unilateral section of the spinal cord affecting the rubrospinal tract; one group was subsequently treated with an antibody neutralizing Nogo-A; the second group received a control antibody. Intact animals were also included in the study. Counting neurons stained with a monoclonal antibody recognizing non-phosphorylated epitopes on neurofilaments (SMI-32) indicated that their number in the contralesional RNm was consistently inferior to that in the ipsilesional RNm, in a proportion amounting up to 35%. The lesion also induced shrinkage of the soma of the neurons detected in the contralesional RNm. Infusing an anti-Nogo-A antibody at the site of the lesion did not increase the proportion of SMI-32 positive rubrospinal neurons in the contralesional RNm nor prevent shrinkage.

Symmetristen komponenttien mallinnus

Tässä insinöörityössä suunniteltiin Helsingin ammattikorkeakoululle jakeluverkoissa tapahtuvien oikosulkujen symmetristen komponenttien laskutavan havainnollistamiseen sopiva sijaiskytkentä. Sijaiskytkennässä tärkeitä huomioitavia asioita olivat mm. jännitetaso, havainnollistavien muuntajien oikosulkukestoisuus, jatkokäyttö laboratoriotyönä ja yleinen havainnollistavuus. Työssä on aluksi perehdytty symmetristen komponenttien ja jakeluverkoissa tapahtuvien oikosulkujen teoriaan. Tämän jälkeen mitoitettiin tarvittavan kytkennän komponenttien jännite- ja virtakestoisuudet mahdolliset lisäkäytöt huomioiden. Näiden rajoitusten mukaan perusteella työtä ruvettiin toteuttamaan. Työssä tilattiin sähkön 40 V:n pääjännitetasolle alentava muuntaja syöttämään oikosulun kestävää muuntajaa, jolla simuloitiin jakeluverkon yleisimpiä vikatyyppejä. Jälkimmäiselle muuntajalle mitoitettiin ja hankittiin sisäistä impedanssia vastaava induktanssi. Tämän avulla rakennettiin kokonaisuus, jonka avulla voidaan simuloida kaikkia tapahtuvia oikosulkuja vastaavat sijaiskytkennät. Työhön jätettiin kehittämisvaraa ja muita laboratoriotyön rakentamismahdollisuuksia tulevien insinööritöiden tekijöille.

Organizing principles across the senses

ABSTRACT This thesis is composed of two main parts. The first addressed the question of whether the auditory and somatosensory systems, like their visual counterpart, comprise parallel functional pathways for processing identity and spatial attributes (so-called `what' and `where' pathways, respectively). The second part examined the independence of control processes mediating task switching across 'what' and `where' pathways in the auditory and visual modalities. Concerning the first part, electrical neuroimaging of event-related potentials identified the spatio-temporal mechanisms subserving auditory (see Appendix, Study n°1) and vibrotactile (see Appendix, Study n°2) processing during two types of blocks of trials. `What' blocks varied stimuli in their frequency independently of their location.. `Where' blocks varied the same stimuli in their location independently of their frequency. Concerning the second part (see Appendix, Study n°3), a psychophysical task-switching paradigm was used to investigate the hypothesis that the efficacy of control processes depends on the extent of overlap between the neural circuitry mediating the different tasks at hand, such that more effective task preparation (and by extension smaller switch costs) is achieved when the anatomical/functional overlap of this circuitry is small. Performance costs associated with switching tasks and/or switching sensory modalities were measured. Tasks required the analysis of either the identity or spatial location of environmental objects (`what' and `where' tasks, respectively) that were presented either visually or acoustically on any given trial. Pretrial cues informed participants of the upcoming task, but not of the sensory modality. - In the audio-visual domain, the results showed that switch costs between tasks were significantly smaller when the sensory modality of the task switched versus when it repeated. In addition, switch costs between the senses were correlated only when the sensory modality of the task repeated across trials and not when it switched. The collective evidence not only supports the independence of control processes mediating task switching and modality switching, but also the hypothesis that switch costs reflect competitive interterence between neural circuits that in turn can be diminished when these neural circuits are distinct. - In the auditory and somatosensory domains, the findings show that a segregation of location vs. recognition information is observed across sensory systems and that these happen around 100ms for both sensory modalities. - Also, our results show that functionally specialized pathways for audition and somatosensation involve largely overlapping brain regions, i.e. posterior superior and middle temporal cortices and inferior parietal areas. Both these properties (synchrony of differential processing and overlapping brain regions) probably optimize the relationships across sensory modalities. - Therefore, these results may be indicative of a computationally advantageous organization for processing spatial anal identity information.

La gestió dels llibres electrònics a la Biblioteca virtual de la UOC

El text que es presenta mostra com es du a terme la gestió dels llibres electrònics a la Biblioteca virtual (d'ara endavant BV) de la Universitat Oberta de Catalunya (d'ara endavant UOC). La BV posa un èmfasi especial en l'adquisició de llibres digitals per millorar l'accés als usuaris als recursos i col¿leccions d'una universitat que es caracteritza per la virtualitat. El document presenta, en primer lloc, l'entorn en què s'adquireixen i s'utilitzen els llibres electrònics: s'expliquen els diferents escenaris d'adquisició en els quals es pot trobar la biblioteca i es defineixen els circuits interns que en permeten la gestió i els processos tècnics dels documents. A continuació es mostren les diferents opcions d'accés i consulta de llibres electrònics que actualment s'ofereixen des de la biblioteca i s'expliquen les anàlisis d'usos d'aquests documents. Finalment es presenten les conclusions a les quals arriba la BV sobre el nou context de llibres electrònics.

Radioimmuno positron emission tomography with monoclonal antibodies: a new approach to quantifying in vivo tumour concentration and biodistribution for radioimmunotherapy.

Radioimmunodetection of tumours with monoclonal antibodies is becoming an established procedure. Positron emission tomography (PET) shows better resolution than normal gamma camera single photon emission tomography and can provide more precise quantitative data. Thus, in the present study, these powerful methods have been combined to perform radioimmuno PET (RI-PET). Monoclonal antibodies directed against carcinoembryonic antigen (CEA) an IgG, its F(ab')2 and a mouse-human chimeric IgG derived from it were labelled with 124I, a positron-emitting radionuclide with a convenient physical half-life of four days. Mice, xenografted with a CEA-producing human colon carcinoma, were injected with the 124I-MAb and the tumours were visualized using PET. The concentrations of 124I in tumour and normal tissue were determined by both PET and direct radioactivity counting of the dissected animals, with very good agreement. To allow PET quantification, a procedure was established to account for the presence of radioactivity during the absorption correction measurement (transmission scan). Comparison of PET and tissue counting indicates that this novel combination of radioimmunolocalization and PET (RI-PET) will provide, in addition to more precise diagnosis, more accurate radiation dosimetry for radioimmunotherapy.

A CRTC1 deficient mouse line study : relevance to mood disorders

Summary Mood disorders are among the most prevalent, psychosocial^ debilitating, chronic and relapsing forms of psychiatric illnesses. Despite considerable advances in their characterization, the heterogeneous nature of susceptibility factors and patient's symptoms could account for the lack of totally effective and remissive treatment. The neurobiological hypothesis of mood disorders etiology has evolved since the monoamine and neurotrophin theories and current evidence is pointing toward their integration in a broader polygenic epistatic model resulting in defective neuroplasticity of circuitries involved in emotion processing. Consequently, the unraveling of molecular underpinning pathways involved in neuronal plasticity, commonly altered among mood disorder syndromes and symptoms, should shed light on their etiology and provide new drug target. The transcription factor CREB has been critically involved in the long-lasting forms of neuronal plasticity and in the regulation of several mood disorders susceptibility genes. In addition, altered CREB activity has been associated with mood disorders pathophysiology and pharmacotherapy. Interestingly, the newly-identified protein CREB-regulated transcription coactivator 1 (CRTC1) was shown by previous studies in the laboratory to be a neuroactivity- dependent cAMP and calcium sensor, a potent activator of CREB-dependent transcription and involved in neuroplasticity mechanisms associated with long-term synaptic potentiation. Furthermore, the major mood disorder susceptibility gene Bdnf was suggested to be transcriptional regulated by CRTC1. Therefore, we aimed to investigate a role for CRTC1 in mood disorders by generating and characterizing a Crtcl deficient mouse model at the behavioral and molecular levels. Interestingly, their comprehensive characterization revealed a behavioral profile mirroring several major symptoms comorbid in mood disorders, including altered social interactions, aggressive behaviors, obesity, psychomotor retardation, increased emotional response to stress, decreased sexual drive and depression-like behaviors. To investigate the molecular mechanisms underlying these pathological behaviors and the implication of CRTC1 in the regulation of CREB-regulated genes in vivo, we also quantified transcript levels of several relevant CREB-regulated susceptibility genes in brain structures involved in the pathophysiology of mood disorders. Strikingly, we found the underexpression of primary components of the neurotrophin system: Bdnf and its cognate receptor TrkB, a marked decrease in the Nr4a family of transcription factors, implicated in neuroplasticity and associated with dopamine-related disorders, as well as in several other relevant CREB regulated genes. Moreover, neurochemical analysis revealed that Crtcl null mice presented alteration in prefrontal cortical monoamine turnover as well as in hippocampal and accumbal serotonin levels, similarly associated with mood disorders etiology and pharmacotherapy. Together, the present thesis supports the involvement of CRTC1 pathway hypofunction in the pathogenesis of mood disorders and specifically in pathological aggression, obesity and depression-related behavior comorbidities. Ultimately, CRTC1 may represent an interesting antidepressant, antiaggressive or mood stabilizer drug target candidate through the modulation of major CREB regulated susceptibility genes. Les troubles de l'humeur comptent parmi les maladies psychiatriques les plus prévalentes, psychosocialement débilitantes, chroniques et avec le plus grand risque de rechute. Malgré de considérable avancées dans leur caractérisation, la nature hétérogène des facteurs de susceptibilité et des symptômes présentés par les patients, semble justifier l'absence de traitement entraînant une rémission complète de la maladie. L'hypothèse de l'étiologie neurobiologique des troubles de l'humeur a évolué depuis la théorie des monoamines et des neurotrophines. Actuellement, elle tend à les englober dans un modèle polygénique épistatique induisant une déficience de la neuroplasticité des circuits impliqué dans la régulation des émotions. Par conséquent, il apparaît particulièrement relevant de caractériser des voies moléculaires impliquées dans la plasticité neuronale, communément altérées parmi les différents syndromes et symptômes des maladies de l'humeur, afin d'améliorer leur compréhension ainsi que de proposer de nouvelles cibles thérapeutiques potentielles. Le facteur de transcription CREB a été de façon répétée et cohérente impliqué dans les mécanismes à long terme de la plasticité neuronale, ainsi que dans la régulation de plusieurs gènes de susceptibilité aux maladies de l'humeur. De plus, une altération dans l'activité de CREB a été impliqué dans leur étiologie et pharmacothérapie. De façon intéressante, des résultats préliminaires sur la protéine récemment découverte CREB-regulated transcription coactivator 1 (CRTC1) ont indiqué que son activation était dépendante de l'activité neuronale, qu'il était un senseur du calcium et de l'AMPc, ainsi qu'un coactivateur de CREB requis et puissant impliqué dans les mécanismes de plasticité neuronale associés à la potentialisation à long terme. En outre, des résultats ont suggéré que le gène majeur de susceptibilité Bdnf est régulé par CRTC1. Ainsi, notre objectif a été d'investiguer un rôle éventuel de CRTC1 dans les maladies de l'humeur en générant et caractérisant une lignée de souris déficiente pour Crtcl, tant au niveau comportemental que moléculaire. De façon intéressante, leur caractérisation détaillée a révélé un profil comportemental reflétant de nombreux aspects des maladies de l'humeur incluant une altération des interactions sociales, une agression pathologique, l'obésité, un retard psychomoteur, une réponse émotionnelle au stress accrue, une diminution de la motivation sexuelle, et des comportements reliés à la dépression. Afin d'investiguer les mécanismes moléculaires sous- jacents cette altération du comportement, ainsi que l'implication de CRTC1 dans l'expression des gènes régulés par CREB in vivo, nous avons quantifié les niveaux de transcrits de plusieurs gènes de susceptibilité régulés par CREB et impliqués dans la physiopathologie des maladies de l'humeur. Remarquablement, nous avons trouvé la sous-expression de composants primordiaux du système neurotrophique: Bdnf et son récepteur TrkB, une diminution majeure de la famille des facteurs de transcription Nr4a, impliqués dans la neuroplasticité et associés à des désordres liés à la dopamine, ainsi que de nombreux autres gènes relevants régulés par CREB. De plus, une analyse neurochimique a révélé que les souris déficientes pour Crtcî présentent une altération du turn-over des monoamines du cortex préfrontal ainsi que des niveaux hippocampaux et accumbaux de sérotonine, associés de façon similaire dans l'étiologie et la pharmacothérapie des maladies de l'humeur. Vue dans son ensemble, la présente thèse supporte l'implication d'une sous-régulation de la voie de CRTCI dans la pathogenèse des maladies de l'humeur ainsi que dans la comorbidité de l'agression pathologique, l'obésité et la dépression. En conclusion, CRTCI pourrait représenter une cible médicamenteuse intéressante aux propriétés antidépressante, antiagressive ou stabilisatrice de l'humeur au travers de la modulation de gènes de susceptibilité majeurs régulés par CREB.

Merger failures

This paper proposes an explanation as to why some mergers fail, based on the interactionbetween the pre- and post-merger processes. We argue that failure may stem from informationalasymmetries arising from the pre-merger period, and problems of cooperation andcoordination within recently merged firms. We show that a partner may optimally agree tomerge and abstain from putting forth any post-merger effort, counting on the other partnerto make the necessary efforts. If both follow the same course of action, the merger goesahead but fails. Our unique equilibrium allows us to make predictions on which mergers aremore likely to fail.

Zapfen-Stäbchen-Dystrophie durch eine neue reinerbige RPE65-Mutation in Leberscher kongenitaler Amaurose Cone-Rod Dystrophy Caused by a Novel Homozygous RPE65 Mutation in Leber Congenital Amaurosis.

Background: The aim of this study was to describe an unexpected phenotype in a family with Leber congenital amaurosis (LCA) due to a retinal pigment epithelium-specific protein 65 kDa (RPE65) homozygous mutation. History and Signs: We analyzed a family from Yemen in which 3 individuals were affected with LCA. Linkage analysis using markers flanking the known LCA genes was done, followed by direct sequencing of RPE65. Therapy and Outcome: Severe visual impairment and night blindness were observed during infancy. We observed photophobia only in the 8-year-old patient. The youngest affected had bilateral hyperopia of + 3.50 and visual acuity of 1/60. The oldest two had visual acuity limited to hand movements in the right eye (OD) and counting fingers in the left eye (OS) for the oldest and of 5/60 OD, 6/60 OS for the other. They showed disc pallor, attenuated vessels, white flecks in the retina mid-periphery and bull's eye maculopathy. ERGs of the oldest child were completely unresponsive. Genomic sequencing identified a novel homozygous missense mutation, IVS2-3C > G, in the second RPE65 intron. Conclusions: We identified a novel LCA-related homozygous RPE65 mutation associated with a severe clinical presentation including an early and severe cone dysfunction. This is in contrast with the presentation associated with other RPE65 mutations predominantly causing rod-cone dystrophy with residual visual function.

Late Proterozoic thrust tectonics, high-pressure metamorphism and Uranium mineralization in the domes area, Lufilian arc, northwestern Zambia

The following main lithostratigraphic units have been distinguished in the Domes Area. The Kibaran basement complex composed of gneisses, migmatites with amphibolite bands and metagranites is exposed in dome structures; metamorphic features of Kibaran age have been almost completely obliterated by extensive Lufilian reactivation. The post-Kibaran cover sequence is subdivided into the Lower Roan Group consisting of well-preserved quartzites with high Mg content, talc-bearing, extremely foliated schists intercalated with pseudo-conglomerates of tectonic origin and the Upper Roan Group including dolomitic marbles with rare stromatolites, metapelites and a sequence of detrital metasediments, with local volcano-sedimentary components and interlayered banded ironstones. The sediments of the Lower Roan Group are interpreted as continental to lagoonal-evaporitic deposits partly converted into the talc-kyanite + garnet assemblage characteristic of ``white schists''. The dolomites and metapelites of the Upper Roan Group are attributed to a carbonate platform sequence progressively subsiding under terrigenous deposits, whilst the detrital metasediments and BIF may be interpreted as a basinal sequence, probably deposited on oceanic crust grading laterally into marbles. Metagabbros and metabasalts are considered as remnants of an ocean-floor-type crustal unit probably related to small basins. Alkaline stocks of Silurian age intruded the post-Kibaran cover. Significant ancestral tectonic discontinuities promoted the development of a nappe pile that underwent high-pressure metamorphism during the Lufilian orogeny and all lithostratigraphic units. Rb-Sr and K-Ar and U-Pb data indicate an age of 700 Ma for the highest grade metamorphism and 500 Ma for blocking of the K-Ar and Rb-Sr system in micas, corresponding to the time when the temperature dropped below 350-degrees-400-degrees-C and to an age of about 400 Ma for the emplacement of hypabyssal syenitic bodies. A first phase of crustal shortening by decoupling of basement and cover slices along shallow shear zones has been recognized. Fluid-rich tectonic slabs of cover sediments were thus able to transport fluids into the anhydrous metamorphic basement or mafic units. During the subsequent metamorphic re-equilibration stage of high pressure, pre-existing thrusts horizons were converted into recrystallized mylonites. Due to uplift, rocks were re-equilibrated into assemblages compatible with lower pressures and slightly lower temperatures. This stage occurs under a decompressional (nearly adiabatic) regime, with P(fluid) almost-equal-to P(lithostatic). It is accompanied by metasomatic development of minerals, activated by injection of hot fluids. New or reactivated shear zones and mylonitic belts were the preferred conduits of fluids. The most evident regional-scale effect of these processes is the intense metasomatic scapolitization of formerly plagioclase-rich lithologies. Uraninite mineralization can probably be assigned to the beginning of the decompressional stage. A third regional deformation phase characterized by open folds and local foliation is not accompanied by significant growth of new minerals. However, pitchblende mineralization can be ascribed to this phase as late-stage, short-range remobilization of previously existing deposits. Finally, shallow alkaline massifs were emplaced when the level of the Domes Area now exposed was already subjected to exchange with meteoric circuits, activated by residual geothermal gradients generally related to intrusions or rifting. Most of the superficial U-showings with U-oxidation products were probably generated during this relatively recent phase.

El nuevo método para la determinación de la fecundidad de la Sardina peruana (Sardinops sagax)

La fecundidad de la sardina peruana, Sardinops sagax, fue determinada por primera vez contando el número de ovoci­tos hidratados. El análisis de varianza mostró que las diferencias entre submuestras tomadas de diferentes áreas del ovario fueron en unos casos significativas al nivel del 5%. Estas diferencias son insignificantes a nivel de la población tomando en consideración la alta variación de la fecundidad entre diferentes hembras del mismo peso.

Temporal distribution of Aedes aegypti Linnaeus (Diptera, Culicidae), in a Hospital in Cuiabá, State of Mato Grosso, Brazil

This study aimed at registering and monitoring the presence of Aedes aegypti in the University Hospital Júlio Muller, Cuiabá-MT, as well as investigating the influence of temperature and rainfall on its temporal distribution and egg densities in ovitraps. The study was performed from April/2007 to March/2008, utilizing ovitraps with 10% of hay infusion and a wood paddle as an oviposition substrate. For surveillance, one ovitrap was placed in each of the 12 points distributed throughout the hospital. Ovitraps were collected monthly at the end of a 5-day installation period. After egg counting, wood paddles were immersed in water to allow larval eclosion for species identification through optical microscopy. Egg Density Index (EDI), Positive Ovitraps Index (POI), and Mean Number of Eggs (MNE) were used for data analysis. The presence of A. aegypti in the hospital was registered throughout the study period, except in July. The MNE was proportionally higher in the internal area (n= 8.47 eggs/paddle) when compared to the external area (n= 5.46 eggs/paddle), and was higher in September/October 2007 and January/February 2008. A significant increase in EDI, POI and MNE was registered in periods where the average temperature was higher, and the increase in POI was also concomitant with an increase in rainfall. The continuous presence of A. aegypti in the hospital throughout the study period, points out the need of including this mosquito in the arthropod control list in this environment. This is particularly important, considering that A. aegypti is an important vector of several arboviroses.

Evolving olfactory systems on the fly.

The detection of odour stimuli in the environment is universally important for primal behaviours such as feeding, mating, kin interactions and escape responses. Given the ubiquity of many airborne chemical signals and the similar organisation of animal olfactory circuits, a fundamental question in our understanding of the sense of smell is how species-specific behavioural responses to odorants can evolve. Recent comparative genomic, developmental and physiological studies are shedding light on this problem by providing insights into the genetic mechanisms that underlie anatomical and functional evolution of the olfactory system. Here we synthesise these data, with a particular focus on insect olfaction, to address how new olfactory receptors and circuits might arise and diverge, offering glimpses into how odour-evoked behaviours could adapt to an ever-changing chemosensory world.

Use of artificial substrates of different colors for oviposition by the brown stink bug Euschistus heros (Hemiptera, Pentatomidae)

Aiming to contribute to a rearing methodology for the brown stink bug, Euschistus heros, in the laboratory, we evaluated oviposition on artificial substrates of different colors. During six days, oviposition was evaluated daily, by counting the total number of eggs, number of clutches, and eggs/clutch. Females laid 12,463 eggs, in 1,677 clutches, resulting in an average of 7.28 ± 0.44 eggs/clutch. Black, brown, and green felt had the most eggs and clutches. The results demonstrated that many colors are suitable as oviposition substrate for E. heros, providing information for the mass rearing of this insect.

Risc cardiovascular en pacients que consulten a urgències d´un hospital general amb un esdeveniment vascular agut

La malaltia cardiovascular és una de les principals causes de morbimortalitat. Els factors de risc cardiovasculars són diversos. Hi ha moltes guies de prevenció clínica i escales de risc. Malgrat l’existència de guies de pràctica clínica i millor identificació dels factors de risc, persisteix l’impacte negatiu cardiovascular. L’estudi enregistra aquests esdeveniments cardiovasculars en pacients que ingressen a urgències, durant tres anys, els factors de risc, els tractaments a l’ingrés i a l’alta i l’evolució i mortalitat durant l’ingrés. Compararà la població que ens ocupa amb d’altres i els tractaments. Detectarà el seguiment de les guies i circuits de millora.