La noche de los asesinos: Text, Staging and Audience

La noche de los asesinos: Text, Staging and Audienc

HIV-1 infection of microglial cells in a reconstituted humanized mouse model and identification of compounds that selectively reverse HIV latency.

Most studies of HIV latency focus on the peripheral population of resting memory T cells, but the brain also contains a distinct reservoir of HIV-infected cells in microglia, perivascular macrophages, and astrocytes. Studying HIV in the brain has been challenging, since live cells are difficult to recover from autopsy samples and primate models of SIV infection utilize viruses that are more myeloid-tropic than HIV due to the expression of Vpx. Development of a realistic small animal model would greatly advance studies of this important reservoir and permit definitive studies of HIV latency. When radiation or busulfan-conditioned, immune-deficient NSG mice are transplanted with human hematopoietic stem cells, human cells from the bone marrow enter the brain and differentiate to express microglia-specific markers. After infection with replication competent HIV, virus was detected in these bone marrow-derived human microglia. Studies of HIV latency in this model would be greatly enhanced by the development of compounds that can selectively reverse HIV latency in microglial cells. Our studies have identified members of the CoREST repression complex as key regulators of HIV latency in microglia in both rat and human microglial cell lines. The monoamine oxidase (MAO) and potential CoREST inhibitor, phenelzine, which is brain penetrant, was able to stimulate HIV production in human microglial cell lines and human glial cells recovered from the brains of HIV-infected humanized mice. The humanized mice we have developed therefore show great promise as a model system for the development of strategies aimed at defining and reducing the CNS reservoir

Anatomical Constraints on Attention: Hemifield Independence Is a Signature of Multifocal Spatial Selection

Previous studies have shown independent attentional selection of targets in the left and right visual hemifields during attentional tracking (Alvarez & Cavanagh, 2005) but not during a visual search (Luck, Hillyard, Mangun, & Gazzaniga, 1989). Here we tested whether multifocal spatial attention is the critical process that operates independently in the two hemifields. It is explicitly required in tracking (attend to a subset of object locations, suppress the others) but not in the standard visual search task (where all items are potential targets). We used a modified visual search task in which observers searched for a target within a subset of display items, where the subset was selected based on location (Experiments 1 and 3A) or based on a salient feature difference (Experiments 2 and 3B). The results show hemifield independence in this subset visual search task with location-based selection but not with feature-based selection; this effect cannot be explained by general difficulty (Experiment 4). Combined, these findings suggest that hemifield independence is a signature of multifocal spatial attention and highlight the need for cognitive and neural theories of attention to account for anatomical constraints on selection mechanisms.Psycholog

Variability in the Quality of Visual Working Memory

Working memory is a mental storage system that keeps task-relevant information accessible for a brief span of time, and it is strikingly limited. Its limits differ substantially across people but are assumed to be fixed for a given person. Here we show that there is substantial variability in the quality of working memory representations within an individual. This variability can be explained neither by fluctuations in attention or arousal over time, nor by uneven distribution of a limited mental commodity. Variability of this sort is inconsistent with the assumptions of the standard cognitive models of working memory capacity, including both slot- and resource-based models, and so we propose a new framework for understanding the limitations of working memory: a stochastic process of degradation that plays out independently across memories.Psycholog

Object-Based Benefits without Object-Based Representations

The organization of visual information into objects strongly influences visual memory: Displays with objects defined by two features (e.g. color, orientation) are easier to remember than displays with twice as many objects defined by one feature (Olson & Jiang, 2002). Existing theories suggest that this ‘object-benefit’ is based on object-based limitations in working memory: because a limited number of objects can be stored, packaging features together so that fewer objects have to be remembered improves memory performance. This view predicts that memory for "packaged features" should be correlated (if you remember one feature of an object you should remember the object’s other features). Counter to this prediction, we show that some object features are stored largely independently. Participants were instructed to remember the colors and orientations of 5 colorful isosceles triangles (five-object condition) or the color of 5 colorful circles and the orientation of 5 black isosceles triangles (ten-object condition). After encoding (1200ms) and retention (900ms), memory was assessed with a continuous report for both features. Critically, participants reported both features of the same item in the five-object condition, allowing us to determine whether features were stored in an integrated fashion. Here we replicate the object-benefit: participants remembered twice as many features when arranged in 5 versus 10 objects. However, in the five-object condition memory for the color and orientation of an object was largely independent—when participants failed to accurately report the color or orientation of an object they were often quite accurate at judging the object's other feature. These results challenge the claim that the object-benefit is driven by the storage of integrated object representations, and require a revision of the concept of object-based memory representations. We propose that working memory is object-based in regard to the factors that enhance performance, but is feature-based at the level of representational failure.Psycholog

SUR1 Receptor Interaction with Hesperidin and Linarin Predicts Possible Mechanisms of Action of Valeriana officinalis in Parkinson.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. A theoretical approach of our previous experiments reporting the cytoprotective effects of the Valeriana officinalis compounds extract for PD is suggested. In addiction to considering the PD as a result of mitochondrial metabolic imbalance and oxidative stress, such as in our previous in vitro model of rotenone, in the present manuscript we added a genomic approach to evaluate the possible underlying mechanisms of the effect of the plant extract. Microarray of substantia nigra (SN) genome obtained from Allen Brain Institute was analyzed using gene set enrichment analysis to build a network of hub genes implicated in PD. Proteins transcribed from hub genes and their ligands selected by search ensemble approach algorithm were subjected to molecular docking studies, as well as 20 ns Molecular Dynamics (MD) using a Molecular Mechanic Poison/Boltzman Surface Area (MMPBSA) protocol. Our results bring a new approach to Valeriana officinalis extract, and suggest that hesperidin, and probably linarin are able to relieve effects of oxidative stress during ATP depletion due to its ability to binding SUR1. In addition, the key role of valerenic acid and apigenin is possibly related to prevent cortical hyperexcitation by inducing neuronal cells from SN to release GABA on brain stem. Thus, under hyperexcitability, oxidative stress, asphyxia and/or ATP depletion, Valeriana officinalis may trigger different mechanisms to provide neuronal cell protection.Fil: Santos, Gesivaldo. Universidade Estadual do Sudoeste da Bahia; BrasilFil: Giraldez Alvarez, Lisandro Diego. Universidade Estadual do Sudoeste da Bahia; BrasilFil: Ávila Rodriguez, Marco. Pontificia Universidad Javeriana; ColombiaFil: Capani, Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; ArgentinaFil: Galembeck, Eduardo. Universidade Estadual de Campinas; BrasilFil: Gôes Neto, Aristóteles. Universidade Estadual de Feira de Santana; BrasilFil: Barreto, George E.. Pontificia Universidad Javeriana; ColombiaFil: Andrade, Bruno. Universidade Estadual do Sudoeste da Bahia; Brasi

Detecting changes in real-world objects: The relationship between visual long-term memory and change blindness

A large body of literature has shown that observers often fail to notice significant changes in visual scenes, even when these changes happen right in front of their eyes. For instance, people often fail to notice if their conversation partner is switched to another person, or if large background objects suddenly disappear.1,2 These 'change blindness' studies have led to the inference that the amount of information we remember about each item in a visual scene may be quite low.1 However, in recent work we have demonstrated that long-term memory is capable of storing a massive number of visual objects with significant detail about each item.3 In the present paper we attempt to reconcile these findings by demonstrating that observers do not experience 'change blindness' with the real world objects used in our previous experiment if they are given sufficient time to encode each item. The results reported here suggest that one of the major causes of change blindness for real-world objects is a lack of encoding time or attention to each object (see also refs. 4 and 5).Psycholog

Explaining human multiple object tracking as resource-constrained approximate inference in a dynamic probabilistic model

Multiple object tracking is a task commonly used to investigate the architecture of human visual attention. Human participants show a distinctive pattern of successes and failures in tracking experiments that is often attributed to limits on an object system, a tracking module, or other specialized cognitive structures. Here we use a computational analysis of the task of object tracking to ask which human failures arise from cognitive limitations and which are consequences of inevitable perceptual uncertainty in the tracking task. We find that many human performance phenomena, measured through novel behavioral experiments, are naturally produced by the operation of our ideal observer model (a Rao-Blackwelized particle filter). The tradeoff between the speed and number of objects being tracked, however, can only arise from the allocation of a flexible cognitive resource, which can be formalized as either memory or attention