O VIVER E O VÍRUS

Em uma perspectiva autobiográfica e interseccional, o presente trabalho versa sobre o prisma em que dois sujeitos vivenciaram os fenômenos pandêmicos. Trata-se de transpor para as palavras os sentimentos e as sensações experenciados. Uma tentativa de elaboração conjunta do atravessamento do real da morte que a pandemia de Covid19 impôs a tod@s nós. Empenhando-se em superar a cristalização sintomática através da arte e do trabalho como vias sublimatórias. Um esforço de sinalizar, através da linguagem, o que estaria para além do desamparo, do medo e da angústia. Palavras-chave: Psicologia; Covid-19; Gênero; Filosofia; Arte

Regulation of signal duration and the statistical dynamics of kinase activation by scaffold proteins

Scaffolding proteins that direct the assembly of multiple kinases into a spatially localized signaling complex are often essential for the maintenance of an appropriate biological response. Although scaffolds are widely believed to have dramatic effects on the dynamics of signal propagation, the mechanisms that underlie these consequences are not well understood. Here, Monte Carlo simulations of a model kinase cascade are used to investigate how the temporal characteristics of signaling cascades can be influenced by the presence of scaffold proteins. Specifically, we examine the effects of spatially localizing kinase components on a scaffold on signaling dynamics. The simulations indicate that a major effect that scaffolds exert on the dynamics of cell signaling is to control how the activation of protein kinases is distributed over time. Scaffolds can influence the timing of kinase activation by allowing for kinases to become activated over a broad range of times, thus allowing for signaling at both early and late times. Scaffold concentrations that result in optimal signal amplitude also result in the broadest distributions of times over which kinases are activated. These calculations provide insights into one mechanism that describes how the duration of a signal can potentially be regulated in a scaffold mediated protein kinase cascade. Our results illustrate another complexity in the broad array of control properties that emerge from the physical effects of spatially localizing components of kinase cascades on scaffold proteins.Comment: 12 pages, 6 figure

The effectiveness of computerized clinical guidelines in the process of care: a systematic review

<p>Abstract</p> <p>Background</p> <p>Clinical practice guidelines have been developed aiming to improve the quality of care. The implementation of the computerized clinical guidelines (CCG) has been supported by the development of computerized clinical decision support systems.</p> <p>This systematic review assesses the impact of CCG on the process of care compared with non-computerized clinical guidelines.</p> <p>Methods</p> <p>Specific features of CCG were studied through an extensive search of scientific literature, querying electronic databases: Pubmed/Medline, Embase and Cochrane Controlled Trials Register. A multivariable logistic regression was carried out to evaluate the association of CCG's features with positive effect on the process of care.</p> <p>Results</p> <p>Forty-five articles were selected. The logistic model showed that Automatic provision of recommendation in electronic version as part of clinician workflow (Odds Ratio [OR]= 17.5; 95% confidence interval [CI]: 1.6-193.7) and Publication Year (OR = 6.7; 95%CI: 1.3-34.3) were statistically significant predictors.</p> <p>Conclusions</p> <p>From the research that has been carried out, we can conclude that after implementation of CCG significant improvements in process of care are shown. Our findings also suggest clinicians, managers and other health care decision makers which features of CCG might improve the structure of computerized system.</p

A correlative and quantitative imaging approach enabling characterization of primary cell-cell communication: Case of human CD4+ T cell-macrophage immunological synapses

Cell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals. We applied this approach to examine a previously uncharacterized immunological synapse, investigating autologous human blood CD4+ T cells and monocyte-derived macrophages (MDMs) forming functional conjugates in vitro. Populations of signaling conjugates were visualized, tracked and analyzed by combining live imaging, calcium recording and multivariate statistical analysis. Correlative immunofluorescence was added to quantify endogenous molecular recruitments at the cell-cell junction. By analyzing a large number of rare conjugates, we were able to define calcium signatures associated with different states of CD4+ T cell-MDM interactions. Quantitative image analysis of immunostained conjugates detected the propensity of endogenous T cell surface markers and intracellular organelles to polarize towards cell-cell junctions with high and sustained calcium signaling profiles, hence defining immunological synapses. Overall, we developed a broadly applicable approach enabling detailed single cell- and population-based investigations of rare cell-cell communication events with primary cells

Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection

In vivo imaging of fibrillar β-amyloid deposits may assist clinical diagnosis of Alzheimer's disease (AD), aid treatment selection for patients, assist clinical trials of therapeutic drugs through subject selection, and be used as an outcome measure. A recent phase III trial of [(18)F]flutemetamol positron emission tomography (PET) imaging in 106 end-of-life subjects demonstrated the ability to identify fibrillar β-amyloid by comparing in vivo PET to post-mortem histopathology. Post-mortem analyses demonstrated a broad and continuous spectrum of β-amyloid pathology in AD and other dementing and non-dementing disease groups. The GE067-026 trial demonstrated 91% sensitivity and 90% specificity of [(18)F]flutemetamol PET by majority read for the presence of moderate or frequent plaques. The probability of an abnormal [(18)F]flutemetamol scan increased with neocortical plaque density and AD diagnosis. All dementia cases with non-AD neurodegenerative diseases and those without histopathological features of β-amyloid deposits were [(18)F]flutemetamol negative. Majority PET assessments accurately reflected the amyloid plaque burden in 90% of cases. However, ten cases demonstrated a mismatch between PET image interpretations and post-mortem findings. Although tracer retention was best associated with amyloid in neuritic plaques, amyloid in diffuse plaques and cerebral amyloid angiopathy best explain three [(18)F]flutemetamol positive cases with mismatched (sparse) neuritic plaque burden. Advanced cortical atrophy was associated with the seven false negative [(18)F]flutemetamol images. The interpretation of images from pathologically equivocal cases was associated with low reader confidence and inter-reader agreement. Our results support that amyloid in neuritic plaque burden is the primary form of β-amyloid pathology detectable with [(18)F]flutemetamol PET imaging

Dynein-Dynactin Complex Is Essential for Dendritic Restriction of TM1-Containing Drosophila Dscam

BACKGROUND: Many membrane proteins, including Drosophila Dscam, are enriched in dendrites or axons within neurons. However, little is known about how the differential distribution is established and maintained. METHODOLOGY/PRINCIPAL FINDINGS: Here we investigated the mechanisms underlying the dendritic targeting of Dscam[TM1]. Through forward genetic mosaic screens and by silencing specific genes via targeted RNAi, we found that several genes, encoding various components of the dynein-dynactin complex, are required for restricting Dscam[TM1] to the mushroom body dendrites. In contrast, compromising dynein/dynactin function did not affect dendritic targeting of two other dendritic markers, Nod and Rdl. Tracing newly synthesized Dscam[TM1] further revealed that compromising dynein/dynactin function did not affect the initial dendritic targeting of Dscam[TM1], but disrupted the maintenance of its restriction to dendrites. CONCLUSIONS/SIGNIFICANCE: The results of this study suggest multiple mechanisms of dendritic protein targeting. Notably, dynein-dynactin plays a role in excluding dendritic Dscam, but not Rdl, from axons by retrograde transport

Aβ Imaging: feasible, pertinent, and vital to progress in Alzheimer’s disease

status: publishe