Folding and Aggregation Are Selectively Influenced by the Conformational Preferences of the α-Helices of Muscle Acylphosphatase

The native state of human muscle acylphosphatase (AcP) presents two alpha-helices. In this study we have investigated folding and aggregation of a number of protein variants having mutations aimed at changing the propensity of these helical regions. Equilibrium and kinetic measurements of folding indicate that only helix-2, spanning residues 55-67, is largely stabilized in the transition state for folding therefore playing a relevant role in this process. On the contrary, the aggregation rate appears to vary only for the variants in which the propensity of the region corresponding to helix-1, spanning residues 22-32, is changed. Mutations that stabilize the first helix slow down the aggregation process while those that destabilize it increase the aggregation rate. AcP variants with the first helix destabilized aggregate with rates increased to different extents depending on whether the introduced mutations also alter the propensity to form beta-sheet structure. The fact that the first alpha-helix is important for aggregation and the second helix is important for folding indicates that these processes are highly specific. This partitioning does not reflect the difference in intrinsic alpha-helical propensities of the two helices, because helix-1 is the one presenting the highest propensity. Both processes of folding and aggregation do not therefore initiate from regions that have simply secondary structure propensities favorable for such processes. The identification of the regions involved in aggregation and the understanding of the factors that promote such a process are of fundamental importance to elucidate the principles by which proteins have evolved and for successful protein design

A rare case of multicentric synchronous bi-frontal glioma in a young female. Diagnostic and therapeutic problems: a case report

Multicentric glioblastoma is a uncommon brain malignant tumour

Disgust Enhances the Recollection of Negative Emotional Images

Memory is typically better for emotional relative to neutral images, an effect generally considered to be mediated by arousal. However, this explanation cannot explain the full pattern of findings in the literature. Two experiments are reported that investigate the differential effects of categorical affective states upon emotional memory and the contributions of stimulus dimensions other than pleasantness and arousal to any memory advantage. In Experiment 1, disgusting images were better remembered than equally unpleasant frightening ones, despite the disgusting images being less arousing. In Experiment 2, regression analyses identified affective impact – a factor shown previously to influence the allocation of visual attention and amygdala response to negative emotional images – as the strongest predictor of remembering. These findings raise significant issues that the arousal account of emotional memory cannot readily address. The term impact refers to an undifferentiated emotional response to a stimulus, without requiring detailed consideration of specific dimensions of image content. We argue that ratings of impact relate to how the self is affected. The present data call for further consideration of the theoretical specifications of the mechanisms that lead to enhanced memory for emotional stimuli and their neural substrates

Drosophila melanogaster acylphosphatase: A common ancestor for acylphosphatase isoenzymes of vertebrate species

AbstractAn open reading frame encoding a putative acylphosphatase was found in Drosophila melanogaster. The corresponding gene product shows 40% identity and 22 additional amino acid residues at the C-terminus as compared to muscle- and common-type human acylphosphatases. Moreover, all the residues involved in the catalytic mechanism of vertebrate enzymes are conserved in the D. melanogaster acylphosphatase. The D. melanogaster protein and a deletion mutant, similar in length to vertebrate acylphosphatases, were produced by cloning the corresponding cDNA in Escherichia coli. The wild-type enzyme is a protein with a well-established three-dimensional fold and a markedly reduced conformational stability as compared to vertebrate isoenzymes. The specific activity of the enzyme is significantly lower than that found in vertebrate enzymes though the substrate binding capability is basically unaltered. The deletion of 22 residues does not cause a significant change in kcat, while affecting the apparent binding parameters. This work suggests that the genes encoding the vertebrate enzymes originate from an ancestor gene by duplication and subsequent evolution

Proliferation versus migration in platelet-derived growth factor signaling: the key role of endocytosis.

It is common knowledge that platelet-derived growth factor (PDGF) is a critical regulator of mesenchymal cell migration and proliferation. Nevertheless, these two cellular responses are mutually exclusive. To solve this apparent contradiction, we studied the behavior of NIH3T3 fibroblasts in response to increasing concentrations of PDGF. We found that there is strong cell proliferation induction only with PDGF concentrations >5 ng/ml, whereas the cell migration response arises starting from 1 ng/ml and is negligible at higher PDGF concentrations. According to these phenotypic evidences, our data indicate that cells display a differential activation of the main signaling pathways in response to PDGF as a function of the stimulation dose. At low PDGF concentrations, there is maximal activation of signaling pathways linked to cytoskeleton rearrangement needed for cell motility, whereas high PDGF concentrations activate pathways linked to mitogenesis induction. Our results suggest a mechanism by which cells switch from a migrating to a proliferating phenotype sensing the increasing gradient of PDGF. In addition, we propose that the cell decision to proliferate or migrate relies on different endocytotic routes of the PDGF receptor in response to different PDGF concentrations

A rare case of multicentric synchronous bi-frontal glioma in a young female. Diagnostic and therapeutic problems: a case report

Multicentric glioblastoma is a uncommon brain malignant tumour

Points in Mental Space: an Interdisciplinary Study of Imagery in Movement Creation

As part of a programme of research that is developing tools to enhance choreographic practice, an interdisciplinary team of cognitive scientists, neuroscientists and dance professionals collaborated on two studies examining the mental representations used to support movement creation. We studied choreographer Wayne McGregor’s approach to movement creation through tasking, in which he asks dancers to create movement in response to task instructions that require a great deal of mental imagery and decision making. In our first experiment, we used experience sampling methods (self-report scales and reports about the current focus of thought) with the full company of Wayne McGregor | Random Dance to describe what the dancers report thinking about while creating movement, and to establish how their experiences change as a function of different task conditions. In particular, we contrasted a conventional ‘active’ condition (where dancers are free to move around) with a ‘static’ condition (where they have to create movement mentally, without moving), because all neuroimaging studies of dance require participants to lie motionless within a scanner. We adapted the static mode from Experiment 1 for the neuroimaging session in Experiment 2. Here we recorded the brain activity of an experienced dancer from Wayne McGregor | Random Dance while she mentally undertook movement creation tasks similar to those used in our experience sampling experiment. Both studies involved imagery tasks of a primarily spatial-praxic nature (involving an imagined object or volume that could be approached and manipulated) and imagery that focused on content invoking emotional narratives. In the first study, the dancers’ awareness was focused more than they had anticipated upon conceptual rather than physical or bodily aspects. The very act of reflecting on, and categorising, their experiences provided the dancers with insights about their mental habits during innovative movement creation. Such insights provide conditions under which habits can be recognised and then altered to adopt alternative points in mental space from which to create movement material. Providing the dancers and McGregor with a means to communicate more productively about the properties of the task-based instructions has been acknowledged by the company to be of clear benefit and a useful addition to their working process. In the second study we assessed the feasibility of using fMRI to study the neural underpinnings of choreographing movement tasks. The experiment enabled us to compare brain activity in imagery and movement creation. The data raise some key questions Points in Mental Space 3 concerning the mental context in which such thinking occurs and, given the clear limitations of the current fMRI and experience sampling work, how future research might usefully be directed. Taken together, these two exploratory studies indicate that the experiential and neural attributes of imagery during movement creation are open to systematic investigation: innovative movement creation can start from alternative points in mental, as well as physical, space. This enables us to look forward to establishing with greater precision how tasks that challenge dancers in different ways may affect mental and neural processes and how variation in imagery use across dancers might contribute to the variety of movement creation that they produce. Notably, the act of reflecting on the experience of movement creation also offers some practical leverage to help dancers develop a wider range of strategies for innovation. These findings are being used to contribute to further work informing the development of personal, notebook-like, Choreographic Thinking Tools

Visible to infrared diamond photonics enabled by focused femtosecond laser pulses

Diamond's nitrogen-vacancy (NV) centers show great promise in sensing applications and quantum computing due to their long electron spin coherence time and because they can be found, manipulated, and read out optically. An important step forward for diamond photonics would be connecting multiple diamond NVs together using optical waveguides. However, the inertness of diamond is a significant hurdle for the fabrication of integrated optics similar to those that revolutionized silicon photonics. In this work, we show the fabrication of optical waveguides in diamond, enabled by focused femtosecond high repetition rate laser pulses. By optimizing the geometry of the waveguide, we obtain single mode waveguides from the visible to the infrared. Additionally, we show the laser writing of individual NV centers within the bulk of diamond. We use μ-Raman spectroscopy to gain better insight on the stress and the refractive index profile of the optical waveguides. Using optically detected magnetic resonance and confocal photoluminescence characterization, high quality NV properties are observed in waveguides formed in various grades of diamond, making them promising for applications such as magnetometry, quantum information systems, and evanescent field sensors

Propriedades térnicas de géis e xerogéis híbridos de sílica/orgânico à base de GPTS-TEOS com diferentes concentrações de GPTS

In the present work the thermal characteristics of gels and xerogels of Silica/organic hybrids derived from different concentrations of GPTS-TEOS were investigated by thermal analysis (TG, DTA, and DSC). The preparation of gels of the Silica/organic hybrid matrix was held through the sol-gel process, consisting by the hydrolysis of alkoxides GPTS and TEOS in proportion (1:1) and (1:2) that was promoted in acidic conditions under reflux and stirring at 80oC/2h, producing the matrix in the colloidal state (sol). Gels were prepared by addition of NH4OH to the sol, promoting gelation of sol in sealed plastics containers. Part of the gels samples was analyzed by TG, DTS and DSC techniques in order to characterize water loss and degradation of the polymeric “epoxy” groups present in the structure of the silica derived from the GPTS alkoxide. Another set of samples was dried at 80oC/48h to obtain xerogels (dried gels) and analyzed by the same techniques. We obtained the characteristics temperatures of the matrix by the techniques DTA, DSC and TG, under measurements of thermal analysis until 800oC and 600oC in case of DSC. By thermal analysis (TG, DTA, and DSC) the main endothermic events (loss of water, melting, pyrolysis) and exothermic events (burning of the polymer) of the GPTS-TEOS matrix were determinedNeste trabalho caracterizamos as propriedades térmicas de géis e xerogéis de GPTS-TEOS em diferentes concentrações. Para a preparação dos géis da matriz híbrida de Sílica/orgânico, através do processo sol-gel, realizou-se a hidrólise dos alcóxidos GPTS+TEOS na proporção (1:1) e (1:2) que foi promovida em meio ácido sob refluxo a 80°C por 2h sob agitação, produzindo a matriz no estado coloidal (sol). Géis foram preparados por adição de base NH4OH ao sol promovendo a gelificação em recipientes plásticos lacrados. Parte das amostras na forma de gel foram analisadas pelas técnicas de TG (termogravimetria), DTA (análise térmica diferencial) e DSC (calorimetria diferencial de varredura) com a finalidade de caracterizar a perda de água e a temperatura de degradação do grupo polimérico “epóxi” presente na estrutura da matriz híbrida proveniente do GPTS, quando submetidas a um aumento gradual de temperatura. Outro conjunto de amostras foi seco a 80 °C/48h para obtenção de xerogéis (géis secos) e analisados pelas mesmas técnicas. Obtivemos as temperaturas características das matrizes híbridas pelas técnicas de DTA, DSC, e TG, por medidas de análises térmicas até 8000C e no caso de DSC até 600 oC. Pelas medidas de TG, determinamos através das curvas experimentais, as regiões principais de perda de massa (água em torno de 100 oC e queima do epóxi de 200 oC a 400 oC). Pelas medidas de DTA (e medidas complementares por DSC) determinamos os principais picos endotérmicos (perda de água, fusão, pirólise) e exotérmicos (queima do polímero) para a matriz de Sílica/orgânico obtida a partir do GPTS-TEOS de maneira satisfatória em relação aos artigos já publicados com matrizes semelhante

Anxiety and the deployment of visual attention over time

Two studies investigated the effects of anxiety on the time course of attention to threatening material. A rapid serial visual presentation (RSVP) paradigm required report of words belonging to a prespecified semantic category with a distractor placed at varying positions preceding the target. Where there was little resemblance in meaning between distractors and targets, threat distractors briefly captured the attention of high state anxious individuals but only after a delay. Where distractors resembled the meaning of the targets, attention was captured more immediately, but processing of threat-related material was concentrated at different points in time as a function of both the degree of semantic resemblance between distractors and target, and state anxiety. The extent to which distractors are salient to the experimental task influences attentional capture and the temporal course of processing. The methodological implications of these results are discussed together with a new hypothesis about the effects of state anxiety on attention