dachshund Potentiates Hedgehog Signaling during Drosophila Retinogenesis

Proper organ patterning depends on a tight coordination between cell proliferation and differentiation. The patterning of Drosophila retina occurs both very fast and with high precision. This process is driven by the dynamic changes in signaling activity of the conserved Hedgehog (Hh) pathway, which coordinates cell fate determination, cell cycle and tissue morphogenesis. Here we show that during Drosophila retinogenesis, the retinal determination gene dachshund (dac) is not only a target of the Hh signaling pathway, but is also a modulator of its activity. Using developmental genetics techniques, we demonstrate that dac enhances Hh signaling by promoting the accumulation of the Gli transcription factor Cubitus interruptus (Ci) parallel to or downstream of fused. In the absence of dac, all Hh-mediated events associated to the morphogenetic furrow are delayed. One of the consequences is that, posterior to the furrow, dac- cells cannot activate a Roadkill-Cullin3 negative feedback loop that attenuates Hh signaling and which is necessary for retinal cells to continue normal differentiation. Therefore, dac is part of an essential positive feedback loop in the Hh pathway, guaranteeing the speed and the accuracy of Drosophila retinogenesis.

Calcium oscillations

Changes in cellular calcium concentration control a wide range of physiological processes, from the subsecond release of synaptic neurotransmitters, to the regulation of gene expression over months or years. Calcium can also trigger cell death through both apoptosis and necrosis, and so the regulation of cellular calcium concentration must be tightly controlled through the concerted action of pumps, channels and buffers that transport calcium into and out of the cell cytoplasm. A hallmark of cellular calcium signalling is its spatiotemporal complexity: stimulation of cells by a hormone or neurotransmitter leads to oscillations in cytoplasmic calcium concentration that can vary markedly in time course, amplitude, frequency, and spatial range. In this chapter we review some of the biological roles of calcium, the experimental characterisation of complex dynamic changes in calcium concentration, and attempts to explain this complexity using computational models. We consider the "toolkit" of cellular proteins which influence calcium concentration, describe mechanistic models of key elements of the toolkit, and fit these into the framework of whole cell models of calcium oscillations and waves. Finally, we will touch on recent efforts to use stochastic modelling to elucidate elementary calcium signal events, and how these may evolve into global signals.

Tools For Spatiotemporally Specific Proteomic Analysis In Multicellular Organisms

The emergence of mass spectrometry-based proteomics has revolutionized the study of proteins and their abundances, functions, interactions, and modifications. However, in a multicellular organism, it is difficult to monitor dynamic changes in protein synthesis in a specific cell type within its native environment. In this thesis, we describe methods that enable the metabolic labeling, purification, and analysis of proteins in specific cell types and during defined periods in live animals. We first engineered a eukaryotic phenylalanyl-tRNA synthetase (PheRS) to selectively recognize the unnatural L-phenylalanine analog p-azido-L-phenylalanine (Azf). Using Caenorhabditis elegans, we expressed the engineered PheRS in a cell type of choice (i.e. body wall muscles, intestinal epithelial cells, neurons, pharyngeal muscles), permitting proteins in those cells -- and only those cells -- to be labeled with azides. Labeled proteins are therefore subject to "click" conjugation to cyclooctyne-functionalized affnity probes, separation from the rest of the protein pool and identification by mass spectrometry. By coupling our methodology with heavy isotopic labeling, we successfully identified proteins -- including proteins with previously unknown expression patterns -- expressed in targeted subsets of cells. While cell types like body wall or pharyngeal muscles can be targeted with a single promoter, many cells cannot; spatiotemporal selectivity typically results from the combinatorial action of multiple regulators. To enhance spatiotemporal selectivity, we next developed a two-component system to drive overlapping -- but not identical -- patterns of expression of engineered PheRS, restricting labeling to cells that express both elements. Specifically, we developed a split-intein-based split-PheRS system for highly efficient PheRS-reconstitution through protein splicing. Together, these tools represent a powerful approach for unbiased discovery of proteins uniquely expressed in a subset of cells at specific developmental stages.

iGrooving: A Generative Music Mobile Application for Runners

iGrooving is a generative music mobile application specifically designed for runners. The application’s foundation is a step-counter that is programmed using the iPhone’s built-in accelerometer. The runner’s steps generate the tempo of the performance by mapping each step to trigger a kick-drum sound file. Additionally, different sound files are triggered at specific step counts to generate the musical performance, allowing the runner a level of compositional autonomy. The sonic elements are chosen to promote a meditative aspect of running. iGrooving is conceived as a biofeedback-stimulated musical instrument and an environment for creating generative music processes with everyday technologies, inspiring us to rethink our everyday notions of musical performance as a shared experience. Isolation, dynamic changes, and music generation are detailed to show how iGrooving facilitates novel methods for music composition, performance and audience participation.

Proposal for Academic Achievement and Permanence of Students in the 7th Grade (1)

This paper analyzes the impact of change processes experienced by many student populations when completing primary education (1st-6th grade) and starting secondary education (7th-11th grade). Based on the research conducted, this paper describes situations and aspects that may result in conditional factors for the student’s adjustment at this level: time-space changes, as well as organizational and dynamic changes that would set the new educational environment and social context in which this new stage will be developed. Such conditional factors that affect learning in incoming students: programs, teaching methodology, learning styles and new evaluation methods will be discussed. As a result of this research, a proposal is presented to facilitate transition from primary to the secondary education. This proposal includes guidelines for awareness and strengthening of pedagogical mediation, which would contribute to the permanence of students from all types of institutions in the education system.  (1) [Translator’s note: The Costa Rican education system is composed of primary education (1st-6th grade) and secondary education (7th-11th grade).]

Dynamic properties of human brain structure: learning-related changes in cortical areas and associated fiber connections.

Recent findings in neuroscience suggest that adult brain structure changes in response to environmental alterations and skill learning. Whereas much is known about structural changes after intensive practice for several months, little is known about the effects of single practice sessions on macroscopic brain structure and about progressive (dynamic) morphological alterations relative to improved task proficiency during learning for several weeks. Using T1-weighted and diffusion tensor imaging in humans, we demonstrate significant gray matter volume increases in frontal and parietal brain areas following only two sessions of practice in a complex whole-body balancing task. Gray matter volume increase in the prefrontal cortex correlated positively with subject's performance improvements during a 6 week learning period. Furthermore, we found that microstructural changes of fractional anisotropy in corresponding white matter regions followed the same temporal dynamic in relation to task performance. The results make clear how marginal alterations in our ever changing environment affect adult brain structure and elucidate the interrelated reorganization in cortical areas and associated fiber connections in correlation with improvements in task performance.

Internal Changes in International New Ventures During Initial Internationalization: Finnish SMEs Operating in Dynamic High-tech Industries

The purpose of this qualitative research is to study how international new ventures change internally during initial internationalization. Based on the analysis of seven INV firms, a framework illustrating this change process, will be developed. This research will also develop earlier theories, and create a solid combination of existing theories to explain the phenomenon. INV firms internationalize more rapidly and aggressively than traditional MNEs. At the same, external and internal drivers cause changes in INVs culture, resources, capabilities, strategic management, and output decisions inside the company. Organizational learning and resource acquisition through international business networks explain how INVs are able to cope with the dynamic high-technology industry and be able to adapt. Internationalization of INVs proceeds through several phases, which may be gone through rapidly due to the network effects and INVs’ special characteristics. The results of this research revealed that INVs internal change process proceeds through four phases; pre-incorporation phase, product development phase, internationalization and growth phase, and maturation phase. INVs culture, resources, capabilities, strategic management, and outputs change significantly during initial internationalization, and INVs develop from small start-ups into fully established companies.

Dynamic epigenetic changes in immune responses to infection in human dendritic cells

La méthylation de l'ADN est une marque épigénétique importante chez les mammifères. Malgré le fait que la méthylation de la cytosine en 5' (5mC) soit reconnue comme une modification épigénétique stable, il devient de plus en plus reconnu qu'elle soit un processus plus dynamique impliquant des voies de méthylation et de déméthylation actives. La dynamique de la méthylation de l'ADN est désormais bien caractérisée dans le développement et dans le fonctionnement cellulaire des mammifères. Très peu est cependant connu concernant les implications régulatrices dans les réponses immunitaires. Pour se faire, nous avons effectué des analyses du niveau de transcription des gènes ainsi que du profilage épigénétique de cellules dendritiques (DCs) humaines. Ceux-ci ont été faits avant et après infection par le pathogène Mycobacterium tuberculosis (MTB). Nos résultats fournissent le premier portrait génomique du remodelage épigénétique survenant dans les DCs en réponse à une infection bactérienne. Nous avons constaté que les changements dans la méthylation de l'ADN sont omniprésents, identifiant 3,926 régions différentiellement méthylées lors des infections par MTB (MTB-RDMs). Les MTB-RDMs montrent un chevauchement frappant avec les régions génomiques marquées par les histones associées avec des régions amplificatrices. De plus, nos analyses ont révélées que les MTB-RDMs sont activement liées par des facteurs de transcription associés à l'immunité avant même d'être infecté par MTB, suggérant ces domaines comme étant des éléments d'activation dans un état de dormance. Nos données suggèrent que les changements actifs dans la méthylation jouent un rôle essentiel pour contrôler la réponse cellulaire des DCs à l'infection bactérienne.

A model of the dynamic relationship between blood flow and volume changes during brain activation

The temporal relationship between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is important in the biophysical modeling and interpretation of the hemodynamic response to activation, particularly in the context of magnetic resonance imaging and the blood oxygen level-dependent signal. Grubb et al. (1974) measured the steady state relationship between changes in CBV and CBF after hypercapnic challenge. The relationship CBV proportional to CBFPhi has been used extensively in the literature. Two similar models, the Balloon (Buxton et al., 1998) and the Windkessel (Mandeville et al., 1999), have been proposed to describe the temporal dynamics of changes in CBV with respect to changes in CBF. In this study, a dynamic model extending the Windkessel model by incorporating delayed compliance is presented. The extended model is better able to capture the dynamics of CBV changes after changes in CBF, particularly in the return-to-baseline stages of the response.

The ionospheric signatures of flux transfer events and solar wind dynamic pressure changes

The generation of flow and current vortices in the dayside auroral ionosphere has been predicted for two processes ocurring at the dayside magnetopause. The first of these mechanisms is time-dependent magnetic reconnection, in “flux transfer events” (FTEs); the second is the action of solar wind dynamic pressure changes. The ionospheric flow signature of an FTE should be a twin vortex, with the mean flow velocity in the central region of the pattern equal to the velocity of the pattern as a whole. On the other hand, a pulse of enhanced or reduced dynamic pressure is also expected to produce a twin vortex, but with the central plasma flow being generally different in speed from, and almost orthogonal to, the motion of the whole pattern. In this paper, we make use of this distinction to discuss recent observations of vortical flow patterns in the dayside auroral ionosphere in terms of one or other of the proposed mechanisms. We conclude that some of the observations reported are consistent only with the predicted signature of FTEs. We then evaluate the dimensions of the open flux tubes required to explain some recent simultaneous radar and auroral observations and infer that they are typically 300 km in north–south extent but up to 2000 km in longitudinal extent (i.e., roughly 5 hours of MLT). Hence these observations suggest that recent theories of FTEs which invoke time-varying reconnection at an elongated neutral line may be correct. We also present some simultaneous observations of the interplanetary magnetic field (IMF) and solar wind dynamic pressure (observed using the IMP8 satellite) and the ionospheric flow (observed using the EISCAT radar) which are also only consistent with the FTE model. We estimate that for continuously southward IMF ( ≈ 5 nT) these FTEs contribute about 30 kV to the mean total transpolar voltage (∼30%).

Time-lag in biological responses to landscape changes in a highly dynamic Atlantic forest region

Time-lagged responses of biological variables to landscape modifications are widely recognized, but rarely considered in ecological studies. In order to test for the existence of time-lags in the response of trees, small mammals, birds and frogs to changes in fragment area and connectivity, we studied a fragmented and highly dynamic landscape in the Atlantic forest region. We also investigated the biological correlates associated with differential responses among taxonomic groups. Species richness and abundance for four taxonomic groups were measured in 21 secondary forest fragments during the same period (2000-2002), following a standardized protocol. Data analyses were based on power regressions and model selection procedures. The model inputs included present (2000) and past (1962, 1981) fragment areas and connectivity, as well as observed changes in these parameters. Although past landscape structure was particularly relevant for trees, all taxonomic groups (except small mammals) were affected by landscape dynamics, exhibiting a time-lagged response. Furthermore, fragment area was more important for species groups with lower dispersal capacity, while species with higher dispersal ability had stronger responses to connectivity measures. Although these secondary forest fragments still maintain a large fraction of their original biodiversity, the delay in biological response combined with high rates of deforestation and fast forest regeneration imply in a reduction in the average age of the forest. This also indicates that future species losses are likely, especially those that are more strictly-forest dwellers. Conservation actions should be implemented to reduce species extinction, to maintain old-growth forests and to favour the regeneration process. Our results demonstrate that landscape history can strongly affect the present distribution pattern of species in fragmented landscapes, and should be considered in conservation planning. (C) 2009 Elsevier Ltd. All rights reserved.

Estimation and evaluation of dynamic properties as indicators of changes on soil structure in sugarcane fields of São Paulo State - Brazil

The indiscriminate management and use of soils without moisture control has changed the structure of it due to the increment of the traffic by agricultural machines through the years, causing in consequence, a soil compaction and yield reduction in the areas of intensive traffic. The purpose of this work was to estimate and to evaluate the performance of preconsolidation pressure of the soil and shear stress as indicators of changes on soil structure in fields cropped with sugarcane, as well as the impact of management processes in an Eutrorthox soil structure located in São Paulo State. The experimental field was located in Piracicaba's rural area (São Paulo State, Brazil) and has been cropped with sugarcane, in the second harvest cycle. The soil was classified by Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA) [Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA), 1999. Centro Nacional de Pesquisa de Solos. Sistema Brasileiro de Classificao de Solos, Empresa Brasileira de Pesquisa Agropecuária (EMBRAPA), Brasilia, 412 pp.] as an Eutrorthox. Undisturbed samples were collected and georeferenced in a grid of 60 m x 60 m from two depths: 0-0.10 m (superficial layer - SL) and in the layer of greatest mechanical resistance (LGMR), previously identified by cone index (CI). The investigated variables were pressure preconsolidation (sigma(p)), apparent cohesion (c) and internal friction angle (phi). The conclusions from the results were that the SLSC was predicted satisfactorily from up as a function of soil moisture; thus, decisions about machinery size and loading (contact pressures) can be taken. Apparent cohesion (c), internal friction angle (phi) and the Coulomb equation were significantly altered by traffic intensity. The sigma(p), c and phi maps were shown to be important tools to localize and visualize soil compaction and mechanical resistance zones. They constitute a valuable resource to evaluate the traffic impact in areas cropped with sugarcane in State of São Paulo, Brazil. (C) 2008 Elsevier B.V. All rights reserved.

Variations in dynamic knee valgus and gluteus medius onset timing in non-athletic females related to hormonal changes during the menstrual cycle

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)